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      Artificial Sperm: New Horizons in Procreation

      review-article
      , M.D. 1 , * , , M.D. 2
      , M.D.
      Rambam Maimonides Medical Journal
      Rambam Health Care Campus
      Artificial sperm, azoospermia, male infertility, spermatogenesis

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          Abstract

          Azoospermia, the absence of any sperm cells from the ejaculated semen, poses a real challenge to the fertility urologist. While there are options to create happy families for azoospermic couples, such as the use of donor sperm and adoption, most couples still want to have genetically related offspring. Advances in urology, gynecology, and fertility laboratory technologies allow surgical sperm retrieval in azoospermic men and achievement of live births for many, but not all azoospermic couples. At present, there are extensive research efforts in several directions to create new fertility options by creating “artificial sperm cells.” While these new horizons are exciting, there are significant obstacles that must be overcome before such innovative solutions can be offered to azoospermic couples. The present review article defines the problem, describes the theoretical basis for creation of artificial genetically related sperm cells, and provides an update on current successes and challenges in the long tortuous path to achieve the ultimate goal: enabling every azoospermic couple to have their own genetically related offspring. Hopefully, these research efforts will ripen in the foreseeable future, resulting in the ability to create artificial sperm cells and provide such couples with off-the-shelf solutions and fulfilling their desire to parent genetically related healthy babies.

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          Most cited references24

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          Review of Azoospermia

          Azoospermia is classified as obstructive azoospermia (OA) or non-obstructive azoospermia (NOA), each having very different etiologies and treatments. The etiology, diagnosis, and management of azoospermia were reviewed and relevant literature summarized. Differentiation between these two etiologies is of paramount importance and is contingent upon thorough history and physical examination and indicated laboratory/genetic testing. OA occurs secondary to obstruction of the male reproductive tract, and is diagnosed through a combination of history/physical examination, laboratory testing, genetics (CFTR for congenital OA), and imaging studies. NOA (which includes primary testicular failure and secondary testicular failure) is differentiated from OA by clinical assessment (testis consistency/volume), laboratory testing (FSH), and genetic testing (karyotype, Y chromosome microdeletion, or specific genetic testing for hypogonadotropic hypogonadism). For obstructive azoospermia, management includes microsurgical reconstruction when feasible using microsurgical vasovasostomy or vasoepididymostomy. Microsurgical epididymal sperm aspiration with in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is utilized for those cases not amenable to reconstruction. NOA management includes medical management for congenital hypogonadotropic hypogonadism and microdissection testicular sperm extraction with IVF/ICSI for appropriate candidates based on laboratory/genetic testing. Overall, this important review provides an updated summary of the most recent available literature describing etiology, diagnosis, and management of azoospermia.
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            Cryopreservation of testicular tissue or testicular cell suspensions: a pivotal step in fertility preservation

            BACKGROUND Germ cell depletion caused by chemical or physical toxicity, disease or genetic predisposition can occur at any age. Although semen cryopreservation is the first reflex for preserving male fertility, this cannot help out prepubertal boys. Yet, these boys do have spermatogonial stem cells (SSCs) that able to produce sperm at the start of puberty, which allows them to safeguard their fertility through testicular tissue (TT) cryopreservation. SSC transplantation (SSCT), TT grafting and recent advances in in vitro spermatogenesis have opened new possibilities to restore fertility in humans. However, these techniques are still at a research stage and their efficiency depends on the amount of SSCs available for fertility restoration. Therefore, maintaining the number of SSCs is a critical step in human fertility preservation. Standardizing a successful cryopreservation method for TT and testicular cell suspensions (TCSs) is most important before any clinical application of fertility restoration could be successful. OBJECTIVE AND RATIONALE This review gives an overview of existing cryopreservation protocols used in different animal models and humans. Cell recovery, cell viability, tissue integrity and functional assays are taken into account. Additionally, biosafety and current perspectives in male fertility preservation are discussed. SEARCH METHODS An extensive PubMED and MEDline database search was conducted. Relevant studies linked to the topic were identified by the search terms: cryopreservation, male fertility preservation, (immature)testicular tissue, testicular cell suspension, spermatogonial stem cell, gonadotoxicity, radiotherapy and chemotherapy. OUTCOMES The feasibility of fertility restoration techniques using frozen-thawed TT and TCS has been proven in animal models. Efficient protocols for cryopreserving human TT exist and are currently applied in the clinic. For TCSs, the highest post-thaw viability reported after vitrification is 55.6 ± 23.8%. Yet, functional proof of fertility restoration in the human is lacking. In addition, few to no data are available on the safety aspects inherent to offspring generation with gametes derived from frozen-thawed TT or TCSs. Moreover, clarification is needed on whether it is better to cryopreserve TT or TCS. WIDER IMPLICATIONS Fertility restoration techniques are very promising and expected to be implemented in the clinic in the near future. However, inter-center variability needs to be overcome and the gametes produced for reproduction purposes need to be subjected to safety studies. With the perspective of a future clinical application, there is a dire need to optimize and standardize cryopreservation and safety testing before using frozen-thawed TT of TCSs for fertility restoration.
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              Men's knowledge, attitudes and behaviours relating to fertility.

              The increasingly common practice in high-income countries to delay childbearing to the fourth and fifth decades of life increases the risk of involuntary childlessness or having fewer children than desired. Older age also increases the risk of age-related infertility, the need for ART to conceive, and obstetric and neonatal complications. Existing research relating to childbearing focusses almost exclusively on women, and in public discourse declining fertility rates are often assumed to be the result of women delaying childbearing to pursue other life goals such as a career and travel. However, evidence suggests that the lack of a partner or a partner willing to commit to parenthood is the main reason for later childbearing.
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                Author and article information

                Journal
                Rambam Maimonides Med J
                Rambam Maimonides Med J
                RMMJ
                Rambam Maimonides Medical Journal
                Rambam Health Care Campus
                2076-9172
                October 2017
                16 October 2017
                : 8
                : 4
                : e0042
                Affiliations
                [1 ]Department of Urology, Rambam Health Care Campus, Haifa, Israel
                [2 ]Neuro-Urology Unit, Rambam Health Care Campus, Haifa, Israel
                Author notes
                [* ]To whom correspondence should be addressed. E-mail: v_shabataev@ 123456rambam.health.gov.il
                Article
                rmmj-8-4-e0042
                10.5041/RMMJ.10319
                5652933
                29059046
                b5b1975c-7737-4f94-83ca-fa02ea03fc7b
                Copyright: © 2017 Shabataev and Tal.

                This is an open-access article. All its content, except where otherwise noted, is distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Special Issue on Novel Technologies in Urologic Investigation and Treatment
                Review Article

                artificial sperm,azoospermia,male infertility,spermatogenesis

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