Abstract
Study question
Is the sperm retrieval rate of a small, pre-processed sample (PPS) of each TESE-biopsy representative for the sperm outcome on the day of ICSI?
Summary answer
The analysis of a PPS reliably reflects the probability of finding comparable numbers of sperm at time of TESE-ICSI.
What is known already
Azoospermia is defined as a condition where no spermatozoa are found in the ejaculate and is diagnosed in up to 15% among infertile men and in 11% of all patients attending our centre. The combination of testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) has become the standard treatment of azoospermic patients. However, no validated standard procedure has been identified to predict the exact sperm outcome of the cryopreserved TESE samples prior to TESE-ICSI so far. For optimal management of TESE-biopsies and the respective ICSI treatment, we developed a stepwise approach for the analysis of tissue samples.
Study design, size, duration
We retrospectively analysed the outcome of 872 microsurgically retrieved testicular biopsies of 198 patients of legal age who had a TESE-ICSI at our department between 2009 and 2019. From all 872 mTESE biopsies the number of sperm extracted from a small, pre-processed sample (PPS) before freezing procedure were known. The PPS was then compared to the number of sperm retrieved from the corresponding thawed specimen on the day of TESE-ICSI.
Participants/materials, setting, methods
During micro-TESE eight samples per testis are retrieved, then 1/10 of each biopsy is removed, digested with collagenase and screened for spermatozoa (pre-processed sample, PPS). If less than 100 spermatozoa are detected the absolute sperm number is recorded, otherwise the result is displayed as the maximum value of 100 sperm. On the day of ICSI, one or more TESE biopsies are thawed and processed for TESE-ICSI; the absolute sperm number is counted again.
Main results and the role of chance
Comparing the sperm yield of 872 TESE samples at time of ICSI to its respective PPS showed a similar sperm outcome with a minor deviation of ± 5 spermatozoa in 73.6% of all biopsies. However, 12.9% of the specimen had less and 13.4% had more spermatozoa. A negative sperm retrieval in the initial PPS was confirmed in 93.1% (268/288). PPS with 1-4 spermatozoa had a 27.2% (43/158) risk of complete absence of sperm on the day of ICSI, yet sperm detection (≥1 sperm) was positive in 72.8% (115/158) of the biopsies. With initially ≥5 spermatozoa present in the PPS, only 0.9% (4/426) of the biopsies had no sperm on the day of ICSI, vice versa 99.1% (422/426) were spermatozoa positive. A significant (p = 0.01) and strong (rs = 0.926) correlation of the sperm retrieval rates of the PPS and the ICSI sample was found meaning that the PPS reflects very well the sperm retrieval rate of the cryopreserved mTESE biopsy thawed at time of TESE-ICSI. However, if ≤ 4 sperm are found in the PPS, there is a relevant risk for a negative sperm retrieval on the day of ICSI and the couple should be carefully advised before start of treatment.
Limitations, reasons for caution
This analysis focussed on sperm prediction in cases of severe male factor infertility and therefore the sperm yield on the day of ICSI was chosen as primary outcome. The reproductive competence of the retrieved sperm in terms of pregnancy and birth rates should be subject to further investigation.
Wider implications of the findings
Treatment options for azoospermic patients are mostly related to the ability to find sperm on the day of ICSI. However, validated standards for sperm processing are missing. Therefore, a PPS seems to be a good option for prediction of sperm retrieval and improves counselling of the patients prior to TESE-ICSI.
Trial registration number
not applicable
Long-term clinical outcomes of testicular sperm extraction and intracytoplasmic sperm injection for infertile men
