Intracytoplasmic sperm injection is not superior to conventional IVF in couples with non-male factor infertility and preimplantation genetic testing for aneuploidies (PGT-A)

Abstract

STUDY QUESTION Does the insemination method impact the euploidy outcome in couples with non-male factor infertility? SUMMARY ANSWER Conventional IVF can be applied in cycles with preimplantation genetic testing for aneuploidies (PGT-A), as both IVF and ICSI generate equal numbers of euploid blastocysts. WHAT IS KNOWN ALREADY Ever since its introduction, the popularity of ICSI has increased tremendously, even in couples with non-male factor infertility. The use of conventional IVF is a contraindication for couples undergoing PGT to ensure monospermic fertilisation and to eliminate potential paternal contamination from extraneous sperm attached to the zona pellucida. Despite this, it has recently been shown that sperm DNA fails to amplify under the conditions used for trophectoderm biopsy samples. STUDY DESIGN, SIZE, DURATION This single-centre prospective pilot study included 30 couples between November 2018 and April 2019. PARTICIPANTS/MATERIALS, SETTING, METHOD Arab couples, with a female age between 18–40 years, body mass index ≤30 kg/m2, at least 10 cumulus oocyte complexes (COCs) following oocyte retrieval (OR) and normal semen concentration and motility (WHO) in the fresh ejaculate on the day of OR, were eligible for the study. Half of the sibling oocytes were assigned to conventional IVF, and the other half were assigned to ICSI. All embryos were cultured in a time-lapse imaging system in Global Total LP media. Blastocysts were subjected to trophectoderm biopsy on Day 5, 6 or 7 and next-generation sequencing (NGS) to determine blastocyst ploidy status. The primary objective was to determine the euploid rate in blastocysts from sibling oocytes. MAIN RESULTS AND THE ROLE OF CHANCE A total of 568 COCs were randomly allocated between IVF (n = 283; 9.4 ± 4.0) and ICSI (n = 285; 9.5 ± 4.1). While the incidence of normal fertilisation per cycle (6.1 ± 3.8 (64.0%) vs 6.3 ± 3.5 (65.4%); P = 0.609) was distributed equally between IVF and ICSI, the degeneration rate (0.1 ± 0.3 vs 0.7 ± 0.8; P = 0.0003) was significantly higher after ICSI and the incidence of abnormal fertilisation (≥3 pronuclei) was significantly higher after IVF (0.9 ± 1.2 vs 0.2 ± 0.4; P = 0.005). For all fertilised oocytes, there were no differences in the number of good-quality embryos on Day 3 (74% vs 78%; P = 0.467), nor in the blastulation rate on Day 5 (80.4% vs 70.8%; P = 0.076). The total number of blastocysts biopsied per cycle on Days 5, 6 and 7 was not significantly different between IVF or ICSI (4.0 ± 2.8 vs 3.9 ± 2.5; P = 0.774). With euploid rates of 49.8 and 44.1% (P = 0.755; OR: 1.05664 [0.75188–1.48494), respectively, there was no significant difference identified between IVF and ICSI (2.0 ± 1.8 vs 1.9 ± 1.7; P = 0.808) and all couples had at least one euploid blastocyst available for transfer. When considering only euploid blastocysts, the male/female ratio was 61/39 in IVF and 43/57 in ICSI (P = 0.063). LIMITATIONS, REASON FOR CAUTION This is a pilot study with a limited patient population of 30 couples (and 568 COCs) with a normal ovarian response. The results of our study should not be extrapolated to other patient populations. WIDER IMPLICATIONS OF THE FINDINGS It is safe to apply conventional IVF in couples with non-male factor infertility undergoing PGT-A. STUDY FUNDING/COMPETING INTEREST(S) No funding was obtained. There are no competing interests. TRIAL REGISTRATION NUMBER NCT03708991.

Monopronucleated (1PN) and tripronuclear (3PN) zygotes formation during assisted reproduction in POSEIDON group 4 patients: Emphasizing on polar bodies

“…The normal fertilization rate in recent publications about nonmale factor ICSI was approximately 50%-71%. 3,17,20,40,41 Our ICSI fertilization rate (75.2%, Table 4) was greater than the competency value of 65%. 28 In addition, in our report, the total fertilization failure rate was even higher in the ICSI group (p = 0.497).…”

“…Even in preimplantation genetic testing for aneuploidy (PGT-A) cycles, or previous total fertilization failure in extremely low oocytes retrieval cycles, IVF can still be the insemination method. 3,16 All couples completed the standard infertility workup. The primary endpoint was the fertilization outcome evaluated by the embryologist 16-18 h post-insemination according to consensus time period.…”

“…1 The assessment of PBs has long been ignored. Previous studies have reported abnormal fertilization rates in assisted reproduction technology, [2][3][4] but little has been reported on PB conditions. Perhaps PBs have not been thoroughly documented because they are often fragmented, difficult to observe and distinguish, and are finally degenerated.…”

“…Despite the lack of robust evidence, ICSI is widely used in infertility cases resulting from nonmale factors, poor ovarian responders (POR), and even unexplained infertility. 3 In Taiwan, ICSI was used in 40.9% (16 287/39 840) of IVF cycles, and of those, cases of male factor infertility accounted for 12.3% in 2018. 13 Even after ICSI, there can be abnormal fertilization observed in addition to fertilization failure.…”

Is Intracytoplasmic Sperm Injection the Solution for all in Unexplained Infertility?

“…Thirty Arab couples were present exhibiting normal semen concentrations and participating in the latest study. 37 An equal distribution existed between ICSI and c-IVF of the number of normal fertilizations per cycle, and c-IVF significantly increased the incidence of abnormal fertilization. On day 3, no difference was found between all fertilized oocytes in terms of the number of good-quality embryos.…”