The assessment of testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) in couples of post chemotherapy non-obstructive azoospermia (NOA)

Abstract

Advances in chemotherapeutic treatments can achieve high remission rates in pediatric and adolescent patients with cancer, but cytotoxic chemotherapy may lead to irreversible spermatogenic dysfunction. In cancer survivors, the restoration of fertility and achievement of paternity have become important concerns, however, at diagnosis, patients with such serious diseases are often not concerned with reproductive issues. A retrospective study in a reproductive center. We evaluated sperm retrieval rate (SRR) of microdissection TESE (micro TESE), two pronuclei (2PN) oocyte rates, blastocyst development rates, good-quality blastocyst (Grade 3BB and above on day 5 by the Gardner scoring) rates, and clinical pregnancy rates per embryo transfer (ET) in 44 cases with post chemotherapy NOA patinets (including 8 patients with bone marrow transplantation (BMT)), 330 NOA cases with 46,XY without past history (unexplained NOA; not including after orchidopexy, Klinefelter syndrome, cryptozoospermia, mumps orchitis, etc), and 107 cases with obstructive azoospermia (OA) between September 2013 and April 2018. The cancer types included testicular cancer, colon cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia, neuroblastoma, and osteosarcoma. The age at micro TESE and chemotherapy was 33.9±5.4 and 17.3±10.4 years of age, respectively, and the wives age at ICSI was 33.7±3.9 years. SRR of micro TESE in post chemotherapy NOA (21/44=47.7%) was higher than unexplained NOA (92/330=27.9%) patients (P<0.01). In sperm retrieved post chemotherapy NOA, age at chemotherapy end was older (20.6±9.1 years) than failure group (14.2±10.8 years) (P<0.05). With respect to type of cancer, there was no predictor for SRR and no significant differences in the pregnancy and live birth rates. In 3 of 8 post BMT patients spermatozoa were successfully retrieved. Two of 3 patients even showed a 46,XX karyotype (transplantation from female donor). The 23 patients who failed to obtain sperm could not find any germ cells in their testicular samples in wet preparations and histopathological sections (Sertoli cell only syndrome). 2PN oocytes, blastocysts development, and good-quality blastocysts rates were 63.2%, 55.8%, and 61.9% in post chemotherapy NOA, 58.3%, 45.2%, and 37.8% in unexplained NOA, and 66.0%, 51.6%, and 42.8% in OA. Post chemotherapy NOA showed higher clinical pregnancy rates per ET (44.9%: 22/49) than unexplained NOA (26.2% : 37/141) (P<0.05). Fourteen children have been born and 4 patients are on going pregnancy in post chemotherapy NOA couples. Age at chemotherapy was important predictive factor for successful sperm recovery. Once sperm were obtained their reproductive performance was satisfactory. These findings provides hope for men of reproductive age who have not undergone sperm cryopreservation before chemotherapy.