Ninety babies born after round spermatid injection into oocytes: survey of their development from fertilization to 2 years of age

Tanaka, Atsushi; Suzuki, Kohta; Nagayoshi, Motoi; Tanaka, Akihiro; Takemoto, Youichi; Watanabe, Seiji; Takeda, Satoru; Irahara, Minoru; Kuji, Naoaki; Yamagata, Zentaro; Yanagimachi, Ryuzo

doi:10.1016/j.fertnstert.2018.04.033

Cited by 54 publications

(59 citation statements)

References 21 publications

(24 reference statements)

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“…A piece of testicular tissue was taken for only histopathologic examination to evaluate stages of spermatogenesis in the absence of mature spermatozoa on mTESE. This information could give as opportunity for future treatment options such as round spermatid injection (ROSI) into oocytes in the presence of late maturation arrest 23 . Additional GCNIS was not examined with the specific immunohistochemical markers.…”

Section: Discussionmentioning

confidence: 99%

Fertility outcomes and predictors for successful sperm retrieval and pregnancy in 327 azoospermic men with a history of cryptorchidism who underwent microdissection testicular sperm extraction

et al. 2020

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Background Although few studies have reported fertility outcomes, no study has reported risk factors that might predict sperm retrieval and pregnancy in azoospermic men with a history of cryptorchidism in a large series. Objectives To investigate fertility outcomes and predictors for successful sperm retrieval and pregnancy in azoospermic men with a history of cryptorchidism who underwent microdissection testicular sperm extraction (mTESE). Materials and methods This retrospective observational study included 327 azoospermic men with a history of cryptorchidism who underwent mTESE. Fertility outcomes including sperm retrieval, fertilization rate, number of transferred embryos, pregnancy, miscarriage, and live birth rates were recorded. Results Sperm retrieval was observed in 172 (52.6%) of the patients. The mean fertilization, pregnancy, and live birth rates were 55.2%±20.5, 53.5%, and 44.8%, respectively. The sperm retrieval rate was significantly higher at the orchidopexy age of ≤ 9.5 years (70.8%) than the orchidopexy age of > 9.5 years (42.1%) (P = .000). Patients with total testicular volume of ≥ 13.75 mL had significantly higher sperm retrieval rate (65.2%) than the patients with total testicular volume of < 13.75 mL (45.5%) (P = .001). Patients with total testosterone level of ≥ 300.5 ng/dL had significantly higher sperm retrieval rate (65.6%) than the patients with total testosterone level of < 300.5 ng/dL (40.3%) (P = .000). Patients with follicle‐stimulating hormone (FSH) level of ≤ 17.25 mIU/ml had significantly higher sperm retrieval rate (72.3%) than the patients with FSH level of > 17.25 mIU/mL (44.4%) (P = .000). Younger male and female ages, and higher fertilization rates were the parameters that might predict pregnancy. Conclusions Infertile azoospermic men with a history of cryptorchidism have high sperm retrieval rate with mTESE. Patients who had orchidopexy at the age of ≤ 9.5 years, and having total testicular volumes of ≥ 13.75 mL with total testosterone level of > 300.5 ng/dL and FSH level of ≤ 17.25 mIU/mL have higher success rate for sperm retrieval.

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Section: Discussionmentioning

confidence: 99%

Fertility outcomes and predictors for successful sperm retrieval and pregnancy in 327 azoospermic men with a history of cryptorchidism who underwent microdissection testicular sperm extraction

et al. 2020

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“…The microinsemination technique was primarily developed by Yanagimachi and colleagues in 1995 using mice 39 . This technique has already been employed to assist human reproduction, and no overt abnormalities have been reported to date 16,17 . A combined technique including testis piece transplantation, RA treatment, and microinsemination might be practical to restore spermatogenesis, especially in prepubertal cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Germ cell depletion in recipient testis has adverse effects on spermatogenesis in orthotopically transplanted testis pieces via retinoic acid insufficiency

Tsuchimoto

Tone

Ogonuki

et al. 2020

Sci Rep

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Germ cell depletion in recipient testes is indispensable for successful transplantation of spermatogonial stem cells. However, we found that such treatment had an adverse effect on spermatogenesis of orthotopically transplanted donor testis tissues. In the donor tissue, the frequency of stimulated by retinoic acid (RA) 8 (STRA8) expression was reduced in germ cells, suggesting that RA signalling indispensable for spermatogenesis was attenuated in germ cell-depleted recipient testes. In this context, germ cell depletion diminished expression of testicular Aldh1a2, which is responsible for testicular RA synthesis, while Cyp26b1, which is responsible for testicular RA metabolism, was still expressed even after germ cell depletion, suggesting an alteration of the RA synthesis/ metabolism ratio. These observations suggested that RA insufficiency was one of the causes of the defective donor spermatogenesis. Indeed, repetitive RA administrations significantly improved donor spermatogenesis to produce fertile offspring without any side effects. These findings may contribute to improving fertility preservation techniques for males, especially to prevent iatrogenic infertility induced by chemotherapy in prepubertal cancer patients. Spermatogonial stem cells (SSCs), a subset of undifferentiated spermatogonia, maintain their population by glial cell line-derived neurotrophic factor (GDNF)-mediated self-renewal 1. Undifferentiated spermatogonia are induced to differentiate into differentiating spermatogonia by retinoic acid (RA). This molecule also mediates the next differentiation step, namely differentiation of differentiating spermatogonia into spermatocytes 2,3. These processes require support from the germline niche consisting of Sertoli and Leydig cells in addition to the basement membrane 4,5. The former cell type was found by Enrico Sertoli as 'nurse cells' for germ cells, which produces GDNF and form a blood-testis barrier, both of which are indispensable for proper spermatogenesis 6. The latter cell type found by Franz Leydig synthesises androgens depending on luteinising hormone to regulate Sertoli cell functions 7. Recent reports have demonstrated that residential macrophages, peritubular myoid cells, and neighbouring lymphatic epithelial cells also have some effects on spermatogenic processes 8-11. Moreover, the hypothalamic-pituitary axis further controls Leydig cell functions via luteinising hormones to produce

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“…Recent reports on the postnatal development of 108 babies born after fertilization of oocytes by round spermatid injection (ROSI), 90 of them in Japan and 18 in Spain [59], did not show any significant differences as compared with naturally conceived babies in either physical or cognitive development during the first 2 years after birth, and none of them developed any of the syndromes associated with genomic imprinting defects [59]. Thus, the use of immature male germ cells for fertilization, in spite of the still relatively low success rates, does not appear to be associated with an increased risk of epigenetic abnormalities in the offspring.…”

Section: Fertilization With Immature Male Germ Cellsmentioning

confidence: 99%

“…As to fertilization by ICSI with immature (testicular) spermatozoa and by round spermatid injection (ROSI), the initial fears that incomplete or defective DNA methylation and chromatin configuration of these immature germ cells might cause syndromes related to genomic imprinting abnormalities [90] were not confirmed. In fact, no increase in the frequency of health problems caused by genomic imprinting abnormalities, such as Beckwith-Wiedemann, Prader-Willi, and Angelman syndromes, has been detected in children born after ICSI with testicular spermatozoa [91] and ROSI [59]. A recent study [92] has suggested that the supposed increase of imprinting errors, present in the sperm of infertile patients, does not have an obvious influence on assisted reproduction outcome or the imprinting of offspring, probably because the imprinting errors in sperm are selectively discarded or corrected during development [20,93].…”

Section: Current Clinical Experiencementioning

confidence: 99%

Paternal Effects on Embryonic, Fetal and Offspring Health: The Role of Epigenetics in the ICSI and ROSI Era

Tesarik

2020

Innovations in Assisted Reproduction Technology

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Paternal effects on the developmental potential of human embryos have been studied since the early 1990s, particularly with respect to newly emerging assisted reproduction technologies. Both genetic and epigenetic paternal effects can influence postfertilization development and cause implantation failure or miscarriage. However, it is only over the last few years that issues related to paternal effects associated with different assisted reproduction techniques on the health status of newborn and adult progeny have been focused. At the same time, new findings point out different, yet unexplored, areas of research into the potentially responsible factors, including the activity of the sperm-derived oocyte-activating factor and the oocyte signaling pathways mediating its action, the methylation status of both imprinted and non-imprinted genes, correct replacement of sperm nuclear protamines with oocyte-derived histones, the histone acetylation status, and the function of sperm-borne small RNAs. It is increasingly important to know how these developmentally important epigenetic regulators can be altered in the context of the current micromanipulation-assisted fertilization techniques, intracytoplasmic sperm injection (ICSI) and round spermatid injection (ROSI). Last but not least, transgenerational transmission of acquired, environmentally conditioned disorders from fathers to offspring is a newly emerging issue which warrants further research.

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Ninety babies born after round spermatid injection into oocytes: survey of their development from fertilization to 2 years of age

Abstract: UMIN Clinical Trials Registry UMIN000006117.

Cited by 54 publications

References 21 publications

Fertility outcomes and predictors for successful sperm retrieval and pregnancy in 327 azoospermic men with a history of cryptorchidism who underwent microdissection testicular sperm extraction

Fertility outcomes and predictors for successful sperm retrieval and pregnancy in 327 azoospermic men with a history of cryptorchidism who underwent microdissection testicular sperm extraction

Germ cell depletion in recipient testis has adverse effects on spermatogenesis in orthotopically transplanted testis pieces via retinoic acid insufficiency

Paternal Effects on Embryonic, Fetal and Offspring Health: The Role of Epigenetics in the ICSI and ROSI Era

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