There is no doubt that couples struggling with infertility choosing to undergo in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) sustain a significant amount of emotional burden associated with navigating the field of reproductive health. In addition, the financial investment can be preclusive and provides an additional layer of stress for couples. There remains no clear set of guidelines on optimizing success of an IVF/ICSI cycle for a couple with primary male factor infertility (MFI) such as the use of ejaculated vs. extracted testicular sperm, testicular vs. epididymal sperm, or fresh vs. frozen sperm. Part of the issue is that there is likely no “one size fits all” approach to the infertile couple. Although there remains no clear consensus on these parameters, some studies are emerging to provide us with tools to have customized counseling conversations with couples to set appropriate expectations.
In this issue, Lee et al. (1) provide their results on retrospective assessment of oocyte to blastocyst attrition rates in couples with MFI, undergoing IVF with ICSI using testicular sperm. Interestingly, they found a lower fertilization rate in all testicular sperm extraction (TESE) patients than in couples using ejaculated sperm. After further categorizing the TESE patients into good, moderate, and poor prognosis tranches by MFI etiology, the investigators found worse blastocyst progression rates in the moderate and poor TESE groups than in controls: 37.7% and 22.1%, respectively, vs. 50.6%.
The discussion surrounding ejaculated vs. extracted testicular sperm is ongoing. As we know, not all oocytes can be fertilized, and not all fertilized embryos become quality blastocysts. Some studies suggest that using sperm extracted from the testis, thus eliminating epididymal travel, reduces oxidative damage and lower DNA fragmentation (2). However, on the flip side, sperm retrieval is not without its own faults, such as procedural risks of TESE, success of extraction, and risks of damage during processing and handling of sperm after extraction. It is difficult to quantify to couples what the benefit of this additional procedure may provide to their fertility success, and there remains confusion on the clinical relevance of elevated DNA fragmentation in IVF/ICSI outcomes in testicular vs. ejaculated sperm (3). Regarding attrition, TESE sperm has been shown to have lower fertilization rates and blastocyst success than ejaculated sperm (4).
Degree of MFI is also an important component of conversations with patients. There is no consensus on impact or even definite correlation of severity of MFI on IVF success because there are many potential confounders, yet patients commonly will ask what their individual chances are. The indeterminate results further support the need for customized conversations with these families.
The findings from this larger sample size study by Lee et al. (1) are clinically significant and allow us to better balance the scales. For one, it is reassuring that there were no differences in fertilization or blastocyst development when comparing the fresh vs. frozen TESE groups. Lower fertilization rates in all TESE groups and worse blastocyst development in the moderate and poor TESE groups suggest that couples with these factors require multiple cycles to build the family they desire. The ability to provide a road map for couples helps to better prepare financially, logistically, and emotionally.
CRediT Authorship Contribution Statement
Rachel Passarelli: Writing – review & editing. Danielle Velez Leitner: Writing – review & editing, Writing – original draft, Conceptualization.
Declaration of Interests
R.P. has nothing to disclose. D.V.L. has nothing to disclose.
References
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