Significant improvements in infertility treatments have led to a reduction in morbidity and mortality among people with complex illnesses. Those people live longer, fuller lives. Advances in assisted reproduction nowadays allow people with complex diseases whose medical conditions or treatments can worsen fertility, to undergo fertility preservation. Fertility preservation options are available for women and men of prepubertal and reproductive age.
In this and the next post, we summarize the available fertility preservation options, including experimental fertility preservation methods, for both sexes. Let us start with male then.
Male testicles function to produce testosterone, a steroid hormone that helps regulate and lead male sexual and reproductive development, as well as spermatozoa, male gamete. Options for fertility preservation exist for pubertal men, and there are some experimental options for fertility preservation for prepubertal males.
Semen cryopreservation, or sperm banking, is the standard fertility intervention for men who have gone through puberty, or who will be sexually mature enough to produce a sperm sample. Appropriate candidates for semen cryopreservation include men who are usually Tanner stage III and/or >12 years of age with 1-2 years of puberty. A sperm sample is collected by masturbation, mechanical ejaculation or electro-ejaculation. Ideally, men will need to provide two samples, about 2-3 days apart. A sperm sample will be analyzed to ensure that the sample actually contains sperm. If spermatozoa are found, the sample may undergo cryopreservation. If spermatozoa are not found, or a person cannot produce a sample, other options should be discussed with the person and his family. Testicular sperm extraction (TESE) is an option for teenagers and adult men who cannot produce a sperm sample. This microsurgical approach involves the extraction of sperm from a testicle biopsy.
The provision of gonadal shielding is an option for men whose treatment is associated with radiotherapy. It is designed to protect the testicles from scattered radiation during treatment.
The only option for prepubertal men who do not produce sperm is cryoconservation of the testicular tissue. This option is considered experimental; but the current consensus is that it is prudent to save testicular tissue for young men at high risk of developing infertility or those who do not have other opportunities to preserve their fertility. Until now, there has been no record of spermatogenic recovery or pregnancies from cryopreserved testicular tissue.
There are several future treatments expected for use with cryopreserved testicular tissue. The first one involves the isolation of spermatogonial stem cells (SSCs) from frozen testicular tissue pieces followed by the transplantation of SSCs into the seminiferous tubules of the person’s testicles for sperm production. This is the only method that can restore normal spermatogenesis, or production of spermatozoa, and fertility in people whose disease or treatment is known to worsen fertility.
Alternative experimental variants of SSCs transplantation include the maturation of spermatozoa in the culture of testicular tissues, as well as autotransplantation or xenotransplantation of testicular tissues. These methods include grafting intact parts of testicular tissue to an orthotopic (scrotum) or ectopic site (e.g., under the skin). Spermatogenesis is initiated, and sperm can be extracted from the tissue in a few weeks. Reconstituted sperm can be used for oocyte fertilization using Intracytoplasmic sperm injection (ICSI).
Future directions for male fertility preservation include an in vitro SSC culture that can generate millions of stem cells for injection into the testicles. This would increase the likelihood of rapid engraftment and the onset of spermatogenesis. In addition, in vitro spermatogenesis has been proposed as a possible way of obtaining sperm from frozen tissues or cells. This option eliminates the need for SSC transplantation or autotransplantation and eliminates the possible re-introduction of malignant cells in people with cancer. The third potential fertility preservation method is the creation of male sex cells derived from pluripotent cells. Somatic cells, such as skin or blood, will be stimulated to produce induced pluripotent stem cells (iPSCs) that can differentiate into transplantable germ cells that can regenerate spermatogenesis. In theory, pluripotent male germ cells would allow males that did not retain sperm or testicle tissue to have biological children.
Alternatively, adoption is an option for men who are infertile or cannot afford egg donation, embryo donation or gestational surrogacy when planning a family, if their fertility has been compromised.