O-043 ICSI: the gamechanger in ART
Authors: Van Steirteghem A 
Published: June 2022

Abstract
On behalf of Neelke De Munck, Herman Tournaye and all colleagues BrusselsIVF (UZBrussel) and Vrije Universiteit Brussel (1980-2022)
In the early years of ART, IVF was successful to alleviate female-factor or idiopathic infertility, yet limited results were obtained in male-factor infertility. In the 80s, assisted fertilization procedures using micromanipulation were introduced, i.e. zona drilling and partial zona dissection. As these procedures did not perform well, at BrusselsIVF we investigated subzonal insemination (SUZI) in mice and eventually we introduced SUZI in our clinic for couples with impaired sperm parameters. IRB approval was obtained in 1991 but required a prospective follow-up protocol of all pregnancies and children born. During SUZI, it occurred that sperm was injected in the oolemma, after which normal fertilization and embryo development was observed. The first pregnancy leading to a live birth in January 1992 was established when 11 oocytes had no fertilization after SUZI but one oocyte was fertilized after “failed SUZI” and was eventually transferred. In the following period, we were able to demonstrate that ICSI was more efficient than SUZI and from July 1993 we only applied ICSI in patients in need of assisted fertilization.
We deliberately choose to share our experience widely with our peers and thereafter ICSI was performed in many centres worldwide and ICSI has been mushrooming. The 2017 ICMART World Report mentions an annual increase of ART cycles with 2 million cycles in 2017 resulting in 330.000 deliveries. The percentage of cIVF versus ICSI is very different depending on the region but on average 70% of cycles are ICSI. This indicates that ICSI is also widely used for non-male infertility. The occurrence of about 15% failed fertilization cycles after cIVF is often the reason for using ICSI. This is for sure the case in countries where only a limited number of cycles is reimbursed by social security or where no reimbursement is in place.
ICSI proved to relieve infertility in couples with severely impaired characteristics of ejaculated sperm including cryptozoospermia. For these patients ICSI results were similar as cIVF for other indications. ICSI with epididymal or testicular sperm could also solve the problem in patients with obstructive azoospermia. Patients with non-obstructive azoospermia can also be helped if sperm cells can be found by testicular sperm extraction using conventional TESE or microTESE. However, the chance to have a child in NOA couples embarking for both TESE and eventually ICSI is much lower if expressed in terms of Intention to Treat: 13,4% in NOA patients and 10,1% in Klinefelter patients. Most of these couples will embark on treatment even after full counselling before considering the use of donor sperm.
At BrusselsIVF, ICSI is also used on in-vitro matured oocytes following culture of immature cumulus-oocyte complexes collected from antral follicles in PCOS patients. For couples undergoing Preimplantation Genetic Testing with biopsy of day-3 cleaving embryos or day-5 or day-6 blastocysts, ICSI is still the preferred procedure in order to avoid contamination at the time of biopsy by remnants of sperm or cumulus cells when cIVF is used.
From the start in 1980 we have invested in clinical, translational and fundamental research. As of now this research is carried out by more than 250 individuals from BrusselsIVF, the centre for reproductive medicine of the UZBrussel and different research units at the VUB. Research focuses on different aspects of infertility, medical genetics, human reproduction, early human development and human pluripotent cells.