Abnormal sperm morphology, so what? The clinical outcome of medical assisted reproduction is not affected by 100% teratospermic semen samples

Abstract Study question What is the success rate (clinical outcome) in medical assisted reproduction (MAR) when 0% normal spermatozoa forms are observed using strict morphology criteria (SMC)? Summary answer Strict criteria morphology has no predictive value for the clinical outcome of MAR. Absence of normal morphology spermatozoa does not preclude high cumulative pregnancy rates. What is known already Many studies have questioned the clinical value of sperm morphology since no effect on treatment outcome is apparent when sperm samples with <4% normal forms are used. However, data evaluating treatment outcome when 0% normal sperm at diagnose (evaluated by strict morphology criteria, WHO 2010) scarce. While teratozoospermia values are known to have a negative correlation with fertilization per cycle, data on cumulative ongoing pregnancy rates (COPR) or live birth rates (LBR) are missing in this selected group. Study design, size, duration This is a retrospective analysis (January 2010-June 2021) of the clinical outcome for couples when the male partner presents with 0% normal morphology (WHO 2010) at diagnostic semen analysis. Cases with 100% globozoospermia, cilia abnormalities or other MMAF phenotypes were excluded. Depending on the total progressively motile sperm count (TPMSC), couples were referred for MAR. The primary outcome presented is COPR/treatment and LBR/couple. Secondary outcomes were total fertilization failure (TFF) and mean fertilization rate (FR). Participants/materials, setting, methods All 193 cases included in this study presented with 100% teratozoospermia, as evaluated by two independent technicians following WHO 2010 manual recommendations. Couples were treated with IUI,IVF or ICSI depending on TPMSC at diagnosis. A total of 17 couples underwent 68 IUI treatments, 20 couples underwent 36 IVF ovum-pickups (OPU) (with respectively fresh embryo transfer (ET) and frozen ET, FET); 156 couples underwent 394 ICSI-OPU (with respectively fresh-ET and FET). Cumulative-OPR per treatment/couple is presented. Main results and the role of chance From the 17 couples undergoing IUI (mean 4 IUI cycles/couple; with or without mild ovarian stimulation) 3 ongoing pregnancies were reported (all singletons; 18% LBR per couple). Twenty IVF couples (mean 1.8 OPUs/couple) resulted in a total of 13 ongoing pregnancies (12 singletons, 1 twin pregnancy), therefore, the LBR per IVF-couple was 65%. In six cycles a TFF was observed even with sufficient motile sperm during insemination (5x with TPMSC >5 x 10^6/ml). If TFF was observed after IVF cycle, then ICSI was performed in the next cycle. The IVF mean %FR using 100% teratozoospermic samples was 54%, compared to 58% in cases with >1% normal forms. Regarding ICSI, 156 couples underwent a total of 377 cycles (mean of 2.4 OPUs/couple). These treatments resulted in a total of 357 fresh-ET and 458 FET. A total of 103 couples achieved 154 ongoing pregnancies (146 singletons, 7 twins), therefore the COPR was 39%/cycle and LBR was 66%/couple. In 13 cycles (3.4%) TFF was observed and in 15 cases the fertilization rate was <20%. The mean FR with ICSI using teratozoospermic samples was 55%. Comparingly, using samples with >1% normal morphology, the laboratory mean for FR is 68% and 3.7% for TFF. Limitations, reasons for caution This is a retrospective study and not matched case-control cohort was used in this analysis. Not all couples have completed 3 complete IVF/ICSI cycles. As not all frozen embryos have been transferred, cumulative pregnancy rates might be higher than the rates reported here. Wider implications of the findings The data presented here confirms the limited value of the actual strict criteria for sperm morphology evaluation. Morphology is important for identification of sporadic sperm samples with atypical malformations such as globozoospermia, MMAF and other aberrant forms of a genetic origin, however SMC evaluation and interpretation should be reconsidered Trial registration number N.A.