Summary Since the establishment of in vitro fertilization, it became evident that almost half of the couples failed to achieve fertilization and this phenomenon was attributed to a male gamete dysfunction. The adoption of assisted fertilization techniques particularly ICSI has been able to alleviate male factor infertility by granting the consistent ability of a viable spermatozoon to activate an oocyte. Single sperm injection, by pinpointing the beginning of fertilization, has been an invaluable tool in clarifying the different aspects of early fertilization and syngamy. However, even with ICSI some couples fail to fertilize due to ooplasmic dysmaturity in relation to the achieved nuclear maturation marked by the extrusion of the first polar body. More uncommon are cases where the spermatozoa partially or completely lack the specific oocyte activating factor. In this work, we review the most relevant aspects of fertilization and its failure through assisted reproductive technologies. Attempts at diagnosing and treating clinical fertilization failure are described.
Germinal vesicle transplantation (GVT) has been proposed as a possible treatment to correct age-related oocyte aneuploidy caused by dysfunctional ooplasm. How healthy ooplasm regulates normal meiosis and subsequent development has yet to be elucidated, but impaired mitochondrial metabolism may be attributable to incomplete segregation of the oocyte chromosomes. In the present study, after ooplasmic mitochondrial damage by photoirradiating chloromethyl-X-rosamine, examination of the oocyte nuclei's ability to survive after transfer into healthy ooplasts was performed. To assess their fertilizability and potential for development, GVT oocytes were fertilized by intracytoplasmic sperm injection (ICSI) and transferred to foster mice. Condition of the offspring at birth was assessed, and epigenetic analysis was performed. Photosensitization consistently inhibited oocyte maturation. However, after GVT of photosensitized nuclei into healthy ooplasts, 67.2% were reconstituted, and 76.2% of these matured normally, with an overall rate of 51.2%, much higher than that (6.0%) in the mitochondrially injured oocytes. After ICSI, 65.8% (52/79) of GVT oocytes were fertilized normally, and 21.1% (11/52) eventually reached the blastocyst stage. The transfer of 132 two-cell GVT embryos into the oviducts of pseudopregnant females resulted in 17 apparently healthy live offspring. For some key developmental genes, a high level of expression was identified in the GVT and ''rescue''-derived fetal adnexa. Thus, one can induce in oocyte mitochondria a photosensitization-based type of damage, which consistently inhibits GV breakdown, meiotic spindle formation, chromosomal segregation, and polar body extrusion. Germinal vesicle transplanted and rescued oocytes were able to undergo maturation, fertilization, and embryonic cleavage and, ultimately, to develop to term. This approach may provide a model with which to study the age-related ooplasmic dysfunction seen in human oocytes.
Transit through the male genital tract did not enhance the ability of ejaculated spermatozoa to achieve fertilization with intracytoplasmic sperm injection compared to that of testicular spermatozoa in men with severely impaired production. In ejaculated samples a lower number of spermatozoa available resulted in an impaired chance of achieving pregnancy. Using testicular spermatozoa may be a reasonable alternative for couples in whom multiple attempts at intracytoplasmic sperm injection have failed using ejaculated sperm from men with cryptozoospermia.
IntroductionSeverely compromised spermatogenesis typical of men with virtual azoospermia or non-obstructive azoospermia requires an extreme search for spermatozoa. Our goal was to evaluate the usefulness of a meticulous search carried out in ejaculated or surgically retrieved specimens in achieving pre- and post-implantation embryo development.Patients and MethodsIn a retrospective cohort study carried out in an academic institution, intracytoplasmic sperm injection (ICSI) outcomes were reviewed as a function of length of microscopic sperm search in ejaculated and surgically retrieved specimens. Couples whose male partner presented with either virtual or non-obstructive azoospermia were treated by ICSI and categorized according to the time spent in identifying and retrieving enough spermatozoa to inject all the oocyte cohort. Semen parameter, fertilization, pregnancies, deliveries, and child welfare in relation to increasing search time were analyzed and compared.Result(s)The maternal and paternal ages were comparable in both ejaculated and testicular sperm extraction (TESE) groups along with the oocytes retrieved. The fertilization rates for both ejaculated and TESE progressively decreased with increasing time (P<0.0001). Clinical pregnancies in the ejaculated cohort remained satifactory. In the TESE cohort, there was a decrease in pregnancy rate with increasing time, from 44% to 23%. In a limited number of cases, offspring health was evaluated in both semen sources and appeared reassuring.Conclusion(s)An extensive and at time exhaustive sperm quest yields kinetically and morphologically impaired spermatozoa without apparent impact on embryo developmental competence. Retrieval of spermatozoa from the seminiferous tubules provided more consistent fertilization and pregnancy outcomes than those retrieved from the ejaculate. A trend indicated that pregnancy rate decreased as search time increased in the TESE group. The utilization of the scarce and unselected spermatozoa did not obviously impair embryo development or cause post-implantation errors.
Notwithstanding the broad success of in vitro fertilization (IVF), a failure to achieve fertilization still plagues a substantial group of patients, with sperm abnormalities the main culprit. In the 1980s, several micromanipulation procedures were adopted from animal husbandry to facilitate gamete interaction, and this resulted in the development of intracytoplasmic sperm injection (ICSI), a procedure through which an oocyte can be fertilized independently of the morphology and/or motility of the single spermatozoon injected. The procedure was first used in cases of fertilization failure after standard IVF or when an inadequate number of sperm cells were available. The consistency of fertilization independent of the functional quality of the spermatozoon has extended the application of ICSI to immature spermatozoa retrieved surgically from the epididymis and testis. Moreover, the need to denude the oocyte has allowed assessment of the nuclear maturity of the oocyte. ICSI is also preferred in conjunction with preimplantation genetic diagnosis and recently has been used to treat HIV discordant couples, where there is a pressing need to minimize the exposure of the oocyte to a large number of spermatozoa. For all ages and with all the different sperm types used, fertilization after ICSI is at approximately 70 to 80% and it ensures a clinical pregnancy rate of up to 45%. These results have made ICSI a procedure comparable in popularity with IVF and have minimized the need for couples suffering from all forms of male infertility to resort to adoption or the use of donor sperm.
The outcome of pregnancy and the developmental wellbeing of children conceived from 12,866 consecutive intracytoplasmic sperm injection (ICSI) cycles was assessed. A total of 3277 couples delivered 5891 neonates. There was a higher than normal incidence of de-novo chromosomal abnormalities in a small sample of ICSI offspring. Controlling for maternal age showed that the incidence of low birth weight and gestational length were comparable with the naturally conceived counterpart. Rates of malformation in ICSI offspring ranged from 3.5 to 6.2%. At 3 years of age (n = 811), the proportion of children at risk for developmental delays was 10.4% in ICSI and 10.7% in IVF singletons. However, high order gestations were characterized by 19.4% of the children having compromised development. Epigenetic analysis of assisted reproductive technique conceptuses found minor imprinted gene expression imbalances. ICSI offspring presented with genetic defects that were inherited or arose de novo. Obstetric and neonatal outcomes of singleton pregnancies appeared to be dependent upon maternal age. ICSI and IVF appeared to exert a negative effect on the wellbeing of offspring mainly because of the association with multiple gestations. All assisted reproduction procedures should be monitored for the eventual effect of environmental aggressors on offspring epigenesis.
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