Poor ovarian reserve and male infertility in a rural in vitro fertilization setup: a case report

Female fertility begins to decline many years prior to the onset of menopause despite continued regular ovulatory cycles. Although there is no strict definition of advanced reproductive age in women, infertility becomes more pronounced after the age of 35. In the female, the number of oocytes decreases with age until the menopause. Oocyte quality also diminishes, due in part to increased aneuploidy because of factors such as changes in spindle integrity. Although older male age affects the likelihood of conception, abnormalities in sperm chromosomes and in some components of the semen analysis are less important than the frequency of intercourse. Age is as accurate as any other predictor of conception with assisted reproductive technology.

Analysis of sperm chromosomes in six carriers of rare and common Robertsonian translocations

Introduction: Robertsonian translocation (RobT) is the central fusion of the long arms of two acrocentric chromosomes, leading to 45 chromosomes in humans. The most common ones are rob(13;14) and rob(14;21) (91%). Other types of RobT are so-called rare cases. In the general population RobTs occur with a frequency of approximately 0.123%, but among men with reproductive failure this value rises 9-fold. Infertility in RobT carriers is associated with the formation of unbalanced spermatozoa resulting from segregation of the chromosomes involved in trivalent during the meiotic prophase. In spermatozoa of many RobT carriers an increased level of chromosomal aneuploidy is observed. Materials and Methods: We examined the hyperhaploidy level of chromosomes 7, 9, 18, 21, 22, X and Y in spermatozoa of 6 RobT unrelated carriers: two carriers with rare rob(13;15), one with rare rob(13;22), and three of the common rob(13;14). Results were compared with the control data from a group of 7 fertile men with a normal karyotype. Fluorescent in situ hybridization (FISH) was applied. Results: We found an increased level of sperm aneuploidy regarding at least one of the analyzed chromosomes in each of the carriers, while in rare RobTs interchromosomal effect (ICE) was observed. Meiotic segregation pattern of a rare rob(13;15) carrier revealed the 76% of normal /balanced spermatozoa. Disucussion: Due to the relatively high population frequency of RobTs, their influence on reproductive failure, hight risk of imbalancement in prenatal diagnosis (7%), and small amount of data for rare RobTs, each newly characterized case is valuable in genetic counseling.

How much, if anything, do we know about sperm chromosomes of Robertsonian translocation carriers?

In men with oligozoospermia, Robertsonian translocations (RobTs) are the most common type of autosomal aberrations. The most commonly occurring types are rob(13;14) and rob(14;21), and other types of RobTs are described as ‘rare’ cases. Based on molecular research, all RobTs can be broadly classified into Class 1 and Class 2. Class 1 translocations produce the same breakpoints within their RobT type, but Class 2 translocations are predicted to form during meiosis or mitosis through a variety of mechanisms, resulting in variation in the breakpoint locations. This review seeks to analyse the available data addressing the question of whether the molecular classification of RobTs into Classes 1 and 2 and/or the type of DD/GG/DG symmetry of the involved chromosomes is reflected in the efficiency of spermatogenesis. The lowest frequency value calculated for the rate of alternate segregants was found for rob(13;15) carriers (Class 2, symmetry DD) and the highest for rob(13;21) carriers (Class 2, DG symmetry). The aneuploidy values for the rare RobT (Class 2) and common rob(14;21) (Class 1) groups together exhibited similarities while differing from those for the common rob(13;14) (Class 1) group. Considering the division of RobT carriers into those with normozoospermia and those with oligoasthenozoospermia, it was found that the number of carriers with elevated levels of aneuploidy was unexpectedly quite similar and high (approx. 70%) in the two subgroups. The reason(s) that the same RobT does not always show a similar destructive effect on fertility was also pointed out.

Human Sperm Chromosomes: To Form Hairpin-Loops, Or Not to Form Hairpin-Loops, That Is the Question

Background: Genomes are non-randomly organized within the interphase nucleus; and spermatozoa are proposed to have a unique hairpin-loop configuration, which has been hypothesized to be critical for the ordered exodus of the paternal genome following fertilization. Recent studies suggest that the hairpin-loop model of sperm chromatin organization is more segmentally organized. The purpose of this study is to examine the 3D organization and hairpin-loop configurations of chromosomes in human spermatozoa. Methods: Three-color sperm-fluorescence in-situ hybridization was utilized against the centromeres, and chromosome p- and q-arms of eight chromosomes from five normozoospermic donors. Wide-field fluorescence microscopy and 3D modelling established the radial organization and hairpin-loop chromosome configurations in spermatozoa. Results: All chromosomes possessed reproducible non-random radial organization (p < 0.05) and formed discrete hairpin-loop configurations. However, chromosomes preferentially formed narrow or wide hairpin-loops. We did not find evidence to support the existence of a centralized chromocenter(s) with centromeres being more peripherally localized than one or both of their respective chromosome arms. Conclusion: This provides further evidence to support a more segmental organization of chromatin in the human sperm nucleus. This may be of significance for fertilization and early embryogenesis as specific genomic regions are likely to be exposed, remodeled, and activated first, following fertilization.

Organization of chromosomes in spermatozoa: an additional layer of epigenetic information?

Elaborate non-random organization of human sperm chromosomes at different structural levels, starting from the DNA packing by protamines up to the higher-order chromosome configuration and nuclear positioning of chromosome territories, has been discovered. Here, we put forward a hypothesis that the unique genome architecture in sperm provides a mechanism for orchestrated unpacking and ordered activation of the male genome during fertilization, thus offering an additional level of epigenetic information that will be deciphered in the descendant cells.

Use of mouse oocytes to evaluate the ability of human sperm to activate oocytes after failure of activation by intracytoplasmic sperm injection

The objective of the present study was to investigate the nuclei of human sperms that failed to fertilize human oocytes after intracytoplasmic sperm injection (ICSI). The sperms were injected into mouse oocytes by a piezo-micromanipulator, and some of these oocytes were artificially activated with strontium chloride (SrCl2) after ICSI. The oocytes were fixed, stained, and subjected to chromosomal analysis. The survival rate of mouse oocytes injected with infertile human sperms was 92.0% (46/50), while that of the control mouse oocytes injected with fertile human sperms was 73.6% (81/110). The rate of two pronuclei (2PN) formation was 0 (0/46) by the infertile sperms and 81.5% (66/81) by the fertile ones, a significant difference (p<0.01). Sperm chromosomes in non-activated oocytes were present as premature chromosome condensation (PCC). Artificial activation after ICSI increased the 2PN formation rate in the infertile group to 90.3% (28/31). The results of the present study suggest that infertile sperms have a low potential to spontaneously activate oocytes and to form pronuclei. Thus, artificial activation after ICSI may rescue oocytes fertilized with infertile human sperms that do not produce 2PN. The present study proved the usefulness of mouse oocytes as specimens in evaluating the oocyte-activating capacity of objective human sperms prior to ICSI treatment.