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PubMed1987

Effects of treatment on fertility in long-term survivors of childhood or adolescent cancer.

In a retrospective cohort study of survivors of cancer and of controls, we estimated the risk of infertility after treatment for cancer during childhood or adolescence. We interviewed 2283 long-term survivors of childhood or adolescent cancer diagnosed in the period from 1945 through 1975, who were identified at five cancer centers in the United States. Requirements for admission to the study were diagnosis before the age of 20, survival for at least five years, and attainment of the age of 21. In addition, 3270 controls selected from among the survivors' siblings were interviewed. Cox regression analysis showed that cancer survivors who married and were presumed to be at risk of pregnancy were less likely than their sibling controls to have ever begun a pregnancy (relative fertility, 0.85; 95 percent confidence interval, 0.78 to 0.92). Radiation therapy directed below the diaphragm depressed fertility in both sexes by about 25 percent. Chemotherapy with alkylating agents, with or without radiation to sites below the diaphragm, was associated with a fertility deficit of about 60 percent in the men. Among the women, there was no apparent effect of alkylating-agent therapy administered alone (relative fertility, 1.02) and only a moderate fertility deficit when alkylating-agent therapy was combined with radiation below the diaphragm (relative fertility, 0.81). Relative fertility in the survivors varied considerably according to sex, site of cancer, and type of treatment; these factors should be taken into consideration in counseling survivors about the long-term consequences of disease.

Adolescent↗
PubMed1995

Micro-assisted fertilization.

In couples who undergo routine in vitro fertilization (IVF), 17% experience significant problems with fertilization and many others are unable to have routine IVF because the quality of their semen is too poor. Often, the only options previously available to these couples were to use sperm donated by fertile men or to remain childless. Micromanipulative assisted fertilization techniques have improved the treatment of severe male factor infertility significantly and this paper provides a brief overview of the recent methodologies. Initially, techniques such as zona drilling and partial zona dissection, in which a hole or slit is placed in the zona pellucida, demonstrated that fertilization and pregnancies could be achieved with semen of very poor quality, but successes were sporadic. Later, subzonal injection of spermatozoa provided more consistent results with many units reporting pregnancies; however, relatively low rates of fertilization (14-34%) and high rates of polyspermy remained unresolved problems. The latest technique, the injection of a single spermatozoon into the oocyte cytoplasm, although technically difficult in animal models, proved to be highly successful in the human, restoring fertilization rates to those seen in routine IVF (65%) and producing good pregnancy rates from transferred embryos. Intracytoplasmic sperm injection has become the method of choice in the treatment of severe male factor infertility and preliminary data suggest that there is no increase in congenital abnormality among babies born after the transfer of injected oocytes.

Animals↗
PubMed1971

Bioelectric responses of the echinoderm egg to fertilization.

The fertilization reaction of echinoderm eggs (Lytechinus pictus, a sea urchin, and Dendraster excentricus, a sand dollar) was followed with intracellular electrodes. Membrane potential and K(+) activity were recorded. The unfertilized egg of Lytechinus has a membrane potential of -8 mV, inside negative. Within 5 sec after the addition of sperm, a fertilization action potential develops, going to +10 mV, inside positive. The time from the initial depolarization to a return to the original -8 mV is 120-150 sec. The repolarization continues until a potential of -10 to -14 mV is reached, at which point it pauses for 3-4 min. At 6-8 min after fertilization, a further and relatively rapid hyperpolarization begins, going to -60 to -65 mV by 15-25 min after fertilization and remaining constant at these values. The membrane potential of the unfertilized egg appears to depend on a general permeability to anions. The fertilization action potential seems to reflect a prolonged influx of sodium. The final depolarization to -60 mV is attributable to the development of potassium conductance. Simultaneous measurements with a K(+) ion-selective electrode gives constant readings of about 240 mM K(+) in the unfertilized eggs throughout the fertilization process. Similar results were obtained with Dendraster eggs. The resting potential of the unfertilized eggs was -7 mV; the action potential on activation attained +18 mV; the repolarization paused at -16 to -24 mV and the final potential attained was -70 mV. The electrical changes after fertilization with spermatozoa or activation with Pronase were identical.

Action Potentials↗
PubMed1977

Release of ovoperoxidase from sea urchin eggs hardens the fertilization membrane with tyrosine crosslinks.

One feature of fertilization is the alteration of the vitelline layer, by components released from the egg, to produce an elevated, covalently crosslinked, hard, insoluble, fertilization membrane. The following evidence indicates that crosslinking and hardening are caused by the production of diand trityrosyl residues, by oxidation of protein-bound tyrosyl residues in the presence of a peroxidase. Hardening of the fertilization membrane, as evidenced by its loss of solubility in 50 mM dithiothreitol, is inhibited by compounds known to inhibit many peroxidases. A peroxidase, here called the ovoperoxidase, is released from eggs at fertilization. This enzyme is inhibited by the same compounds that inhibit hardening and at similar concentrations. Inhibitors of the ovoperoxidase and the hardening reaction include KCN, 3-amino-1,2,4-triazole, NaN(3), phenylhydrazine, K(4)Fe(CN)(6), sodium sulfite, and glycine ethyl ester. In addition, tyramine and N-acetyltyrosine both inhibit hardening, but O-methyltyrosine does not. Dityrosyl and trityrosyl residues are found in acid hydrolysates of isolated, hardened fertilization membranes. These residues have been identified by cellulose phosphate column chromatography, thin-layer chromatography, and amino acid analysis. The amino acid data have been used to estimate that there is one dityrosine crosslink per 55,000 daltons of protein. We suggest that, by catalyzing the crosslinking of tyrosyl residues, the ovoperoxidase leads to the production of a hard fertilization membrane that blocks the entry of additional sperm. Because peroxidases are spermicidal, a secondary function of the enzyme could be to kill sperm in the vicinity of the fertilized egg.

Amino Acids↗
PubMed1978

Hydrogen peroxide production, chemiluminescence, and the respiratory burst of fertilization: interrelated events in early sea urchin development.

After fertilization of the sea urchin, Strongyl-ocentrotus purpuratus, a crosslinked fertilization membrane is formed; the crosslinks (dityrosine residues) are synthesized in a reaction catalyzed by an ovoperoxidase that is released from the cortical granules during fertilization. The substrate for ovoperoxidase activity, hydrogen peroxide, is generated by the egg coincident with the "respiratory burst" that follows parthenogenetic activation by the divalent ionophore A23187 or fertilization. This burst of oxygen consumption may be almost quantitatively accounted for by hydrogen peroxide evolution, as measured by the peroxidase-catalyzed quenching of scopoletin fluorescence. Neither the burst of oxygen consumption nor hydrogen peroxide production occurs when the inhibitor of cortical granule discharge, procaine, is present at fertilization. Fertilization or parthenogenetic activation with A23187 also is associated with a burst of light emission. This chemiluminescence is inhibited in vivo by inhibitors of the ovoperoxidase, such as 3-amino-1,2,4-triazole, phenylhydrazine, sulfite, or azide. A crude ovoperoxidase preparation catalyzes hydrogen peroxide-dependent chemiluminescence that is similarly inhibited. Thus, the bursts of oxygen uptake, peroxide production, and chemiluminescence appear to be several manifestations of the peroxidative system released at fertilization. This system may additionally be responsible for spermicidal activity and thus may act as a component of the block to polyspermy.

Animals↗
PubMed1998

Angiotensin-converting enzyme and male fertility.

The angiotensin-converting enzyme (ACE; EC 3.4.15.1) gene (Ace) encodes both a somatic isozyme found in blood and several other tissues, including the epididymis, and a testis-specific isozyme (testis ACE) found only in developing spermatids and mature sperm. We recently used gene targeting to disrupt the gene coding for both ACE isozymes in mice and reported that male homozygous mutants mate normally but have reduced fertility; the mutant females are fertile. Here we explore the male fertility defect. We demonstrate that ACE is important for achieving in vivo fertilization and that sperm from mice lacking both ACE isozymes show defects in transport within the oviducts and in binding to zonae pellucidae. Males generated by gene targeting that lack somatic ACE but retain testis ACE are normally fertile, establishing that somatic ACE in males is not essential for their fertility. Furthermore, male and female mice lacking angiotensinogen have normal fertility, indicating that angiotensin I is not a necessary substrate for testis ACE. Males heterozygous for the mutation inactivating both ACE isozymes sire wild-type and heterozygous offspring at an indistinguishable frequency, indicating no selection against sperm carrying the mutation.

Animals↗
PubMed2003

The NO pathway acts late during the fertilization response in sea urchin eggs.

Both the inositol 1,4,5-trisphosphate (InsP(3)) and ryanodine receptor pathways contribute to the Ca(2+) transient at fertilization in sea urchin eggs. To date, the precise contribution of each pathway has been difficult to ascertain. Evidence has accumulated to suggest that the InsP(3) receptor pathway has a primary role in causing Ca(2+) release and egg activation. However, this was recently called into question by a report implicating NO as the primary egg activator. In the present study we pursue the hypothesis that NO is a primary egg activator in sea urchin eggs and build on previous findings that an NO/cGMP/cyclic ADP-ribose (cADPR) pathway is active at fertilization in sea urchin eggs to define its role. Using a fluorescence indicator of NO levels, we have measured both NO and Ca(2+) at fertilization and establish that NO levels rise after, not before, the Ca(2+) wave is initiated and that this rise is Ca(2+)-dependent. By inhibiting the increase in NO at fertilization, we find not that the Ca(2+) transient is abolished but that the duration of the transient is significantly reduced. The latency and rise time of the transient are unaffected. This effect is mirrored by the inhibition of cGMP and cADPR signaling in sea urchin eggs at fertilization. We establish that cADPR is generated at fertilization, at a time comparable to the time of the rise in NO levels. We conclude that NO is unlikely to be a primary egg activator but, rather, acts after the initiation of the Ca(2+) wave to regulate the duration of the fertilization Ca(2+) transient.

Animals↗
PubMed1997

Fertility levels and differentials in Beirut during wartime: an indirect estimation based on maternity registers.

In this paper, total fertility estimates for Greater Beirut in the mid-eighties and early nineties are presented, and changes in socio-religious differentials of fertility across time are explored. The baseline information was recorded from registration details for all maternities in Beirut and its inner suburbs in 1984 and 1991: age of mother, number of children ever-born, hospital class, and religion of newborn. An indirect method was used to estimate total fertility from the joint distribution of mothers by age and parity, and, using hospital class as a proxy for social class, differentials in fertility were investigated by Poisson regression. The estimates of total fertility for Beirut shifted from 2.60 in 1984 to 2.52 in 1991, and were higher for Muslims than for Christians in the two periods. The regression analysis showed that: (1) the difference between the two religious groups persisted after control for social class, and in fact applied to the lower social class; (2) fertility dropped between the two dates in the lower social class, and more so for Muslims than for Christians. In comparison with other countries of the region, the decline in Beirut was found to be relatively modest. If the trends assessed in this study were to continue, the religious-based fertility differentials would taper off progressively in the capital city of Lebanon.

Fertility↗
PubMed2005

The path to lowest-low fertility in Ukraine.

The phenomenon of lowest-low fertility, defined as total fertility below 1.3, is now emerging throughout Europe and is attributed by many to postponement of the initiation of childbearing. Here an investigation of the case of Ukraine, where total fertility--1.1 in 2001--is one of the world's lowest, shows that there is more than one pathway to lowest-low fertility. Although Ukraine has undergone immense political and economic transformations in the past decade, it has maintained a young age at first birth and nearly universal childbearing. Analyses of official national statistics and the Ukrainian Reproductive Health Survey show that fertility declined to very low levels without a transition to a later pattern of childbearing. Findings from focus-group interviews are used to suggest explanations of the early fertility pattern. These include the persistence of traditional norms for childbearing and the roles of men and women, concerns about medical complications and infertility at a later age, and the link between early fertility and early marriage.

Adult↗
PubMed2006

Socioeconomic factors, country of birth, and years in Sweden are associated with first birth fertility trends during the 1990s: a national cohort study.

AIMS: Decreasing fertility rates and postponement of first birth are of considerable public health concern in many industrialized countries. Previous studies suggest that this will increase involuntary childlessness in the population. The general aim was to examine the association between sociodemographic factors and first birth fertility trends in Sweden during the 1990s. METHODS: This Swedish national study examined changes in first birth rates and mean age at first birth between 1991 and 1992 (n = 452,000) and 1997-98 (n = 495,756). The impact of socioeconomic factors and years in Sweden on first birth fertility was examined among Swedish-born and 19 subgroups of foreign-born women aged 20-41 years. Poisson regression was used in the analysis. RESULTS: First birth rates decreased and mean age at first birth increased between the two periods among the Swedish-born and most foreign-born women. Non-employment and low income were associated with decreased first birth fertility, and low educational status was associated with slightly increased first birth fertility. Interaction tests revealed that, in contrast to Swedish-born women, several groups of foreign-born women increased their first birth fertility even if they were non-employed or had a low income. Among foreign-born women fewer years in Sweden was significantly associated with increased first birth fertility. CONCLUSION: Public health information should emphasize that postponement of first birth could lead to involuntary childlessness. Health care workers need to consider the woman's socioeconomic characteristics, country of birth, and years in Sweden when such information is given.

Adult↗
PubMed2006

Can 'abnormally' fertilized zygotes give rise to viable embryos?

Conventional practice in in vitro fertilization or intracytoplasmic sperm injection is to select the best quality embryos based on their morphology and cleavage status from a cohort of fertilized oocytes in which two pronuclei were observed at the time they were checked for fertilization. However, in a small proportion of cycles, the selection is limited to embryos that appeared to be either unfertilized (displaying zero pronuclei) or abnormally fertilized (displaying one or three pronuclei) at the time they were checked for fertilization. There is a lack of consensus on whether such embryos should be transferred to the uterus. Cytogenetic analysis of embryos from oocytes with one pronucleus has shown a proportion is diploid. Transfer of such embryos has resulted in healthy births. Limited cytogenetic analysis of oocytes that divide despite the absence of pronuclei at fertilization check indicates that a proportion also have a normal cytogenetic constitution. Cytogenetic analysis of embryos from oocytes with three pronuclei has shown high rates of triploidy and chaotic cell divisions. Subsequent foetuses have extremely unfavourable outcomes. Here, we review the published literature on the cytogenetic analysis of 'unfertilized' and 'abnormally fertilized' embryos and discuss possible pathways which lead to their formation. The limited evidence indicates that oocytes with one pronucleus and oocytes that show normal onward division despite the absence of pronuclei may be considered for replacement in certain circumstances.

Cell Nucleus↗
PubMedDate not supplied

Between nurture and nature: the shifting determinants of female fertility in Danish twin cohorts.

Behaviors related to fertility constitute primary candidates for investigating the relevance of evolutionary influences and biological dispositions on contemporary human behaviors. Using female Danish twin cohorts born 1870-1968, we document important transformations in the relative contributions of "nurture" and "nature" to within-cohort variations in early and complete fertility, and we point toward a systematic relation between the socioeconomic context of cohorts and the relevance of genetic and shared environmental factors. This transformation is most striking for early fertility where genetic factors strengthen over time and are consistent with up to 50 percent of the variation in early fertility in most recent cohorts. Understanding this emerging relevance of genetic factors is of central importance because early fertility constitutes an important determinant of complete fertility levels in low-fertility societies, and because teenage motherhood and early childbearing are often associated with negative life-cycle consequences. Moreover, our results emphasize the need for socially and contextually informed analyses of nature and nurture that allow both factors to influence human reproductive behavior over time.

Adult↗
PubMed2000

Recent trends in Tanzanian fertility.

This paper provides an assessment of the nature and magnitude of Tanzania's recent fertility decline, using robust methods for the identification of fertility trends. A decline in Tanzanian fertility began some time in the late 1970s or early 1980s. The pattern of decline exhibits similarities to patterns identified some years ago in Zimbabwe and Kenya. The decline has been especially marked in urban areas. It has been accompanied by a rapid rise in contraceptive prevalence from the very low levels before 1990 to just under 20 per cent of currently married women of reproductive age. Although falling marital fertility associated with a rise in contraceptive use is the main contributor to the decline in fertility, a rise in the average age at marriage has also made a (smaller) contribution, as has the AIDS epidemic. The fact that fertility is declining in Tanzania raises questions about the social and economic requirements for fertility transitions to begin in sub-Saharan Africa.

Fertility↗
PubMed1991

Identification of a sterility-inducing cytoplasm in a fertile accession line of Phaseolus vulgaris L.

Previous investigations into the genetic mechanism of fertility restoration in cytoplasmic male sterile Phaseolus vulgaris suggested that this is a particularly interesting system for the study of nuclear-mitochondrial interactions. This study was conducted to investigate the nature of nuclear-mitochondrial compatibility in fertile accession line G08063, the reported progenitor to the cytoplasmic male sterile line. Results from genetic analysis indicated that fertile line G08063 carried a sterility-inducing cytoplasm with a fertility restoring nuclear genotype. Mitochondrial DNA analysis indicated that the mechanism of fertility restoration by line G08063 was different from that conditioned by Fr, a previously described restorer gene. A mitochondrial DNA sequence associated with sterility and lost upon fertility restoration by nuclear gene Fr was present in the mitochondrial genome of fertile line G08063; this sequence was not carried within the mitochondrial genome of any other P. vulgaris accession line tested.

Cell Nucleus↗
PubMed1998

Heterosis for viability, fecundity, and male fertility in Drosophila melanogaster: comparison of mutational and standing variation.

If genetic variation for fitness traits in natural populations ("standing" variation) is maintained by recurrent mutation, then quantitative-genetic properties of standing variation should resemble those of newly arisen mutations. One well-known property of standing variation for fitness traits is inbreeding depression, with its converse of heterosis or hybrid vigor. We measured heterosis for three fitness traits, pre-adult viability, female fecundity, and male fertility, among a set of inbred Drosophilia melanogaster lines recently derived from the wild, and also among a set of lines that had been allowed to accumulate spontaneous mutations for over 200 generations. The inbred lines but not the mutation-accumulation (MA) lines showed heterosis for pre-adult viability. Both sets of lines showed heterosis for female fecundity, but heterosis for male fertility was weak or absent. Crosses among a subset of the MA lines showed that they were strongly differentiated for male fertility, with the differences inherited in autosomal fashion; the absence of heterosis for male fertility among the MA lines was therefore not caused by an absence of mutations affecting this trait. Crosses among the inbred lines also gave some, albeit equivocal, evidence for male fertility variation. The contrast between the results for female fecundity and those for male fertility suggests that mutations affecting different fitness traits may differ in their average dominance properties, and that such differences may be reflected in properties of standing variation. The strong differentiation among the MA lines in male fertility further suggests that mutations affecting this trait occur at a high rate.

Alleles↗
PubMed1999

Sperm competition in the absence of fertilization in Caenorhabditis elegans.

Hermaphrodite self-fertilization is the primary mode of reproduction in the nematode Caenorhabditis elegans. However, when a hermaphrodite is crossed with a male, nearly all of the oocytes are fertilized by male-derived sperm. This sperm precedence during reproduction is due to the competitive superiority of male-derived sperm and results in a functional suppression of hermaphrodite self-fertility. In this study, mutant males that inseminate fertilization-defective sperm were used to reveal that sperm competition within a hermaphrodite does not require successful fertilization. However, sperm competition does require normal sperm motility. Additionally, sperm competition is not an absolute process because oocytes not fertilized by male-derived sperm can sometimes be fertilized by hermaphrodite-derived sperm. These results indicate that outcrossed progeny result from a wild-type cross because male-derived sperm are competitively superior and hermaphrodite-derived sperm become unavailable to oocytes. The sperm competition assays described in this study will be useful in further classifying the large number of currently identified mutations that alter sperm function and development in C. elegans.

Animals↗
PubMed1997

Heterogeneity of the zona pellucida carbohydrate distribution in human oocytes failing to fertilize in vitro.

The mammalian zona pellucida contains several glycoproteins whose oligosaccharide moieties are known to play a key role in the interaction with spermatozoa. Since zona pellucida defects may represent one of the most likely causes of failed fertilization in human in-vitro reproduction, we have studied the carbohydrate composition and distribution over the human zona pellucida by means of lectins. Donated, not inseminated cumulus-oocyte complexes, from cohorts with high fertilization rates, and fertilization-failed oocytes from cohorts inseminated with proven fertile donor semen, were analysed using 11 fluorescein-labelled lectins, on deplasticized semi-thin epoxy sections. Results showed that wheat germ agglutinin (WGA), Maclura pomifera (MPA) and Pisum sativum (PSA) bound to the extracellular matrix bordering the zona pellucida-corona radiata interface of cumulus-oocytes complexes, while the zona pellucida was labelled by WGA, Concanavalin A (ConA) and PSA. WGA labelling and correlative electron microscopy on the cumulus-oocyte complexes demonstrated that this lectin is a useful tool to trace the cortical granule distribution in the human oocyte. Surprisingly, in the failed-fertilized oocytes the zona pellucida was also labelled by MPA and showed three different patterns: (i) labelling of the zona pellucida outer surface; (ii) uniform labelling; (iii) labelling of an outer zona pellucida layer with variable thickness. Comparative analysis of WGA and MPA labelling on single failed-fertilized oocytes demonstrated that MPA zona pellucida patterns are not related to the cortical reaction. The nature and meaning of the MPA pattern of failed-fertilized oocytes were discussed in the light of zona pellucida defects impairing sperm receptivity.

Adult↗
PubMed1998

The contribution of subtle oocyte or sperm dysfunction affecting fertilization in endometriosis-associated or unexplained infertility: a controlled comparison with tubal infertility and use of donor spermatozoa.

This study aims to determine the relative contribution of oocyte and/or sperm dysfunction to the reduction of fertilization rates in vitro in cases of minor endometriosis and prolonged unexplained infertility. The results of in-vitro fertilization (IVF) treatment with ovarian stimulation have been compared between couples with the above conditions and women with tubal infertility (as control for oocyte function) and the use of donor spermatozoa (as control for sperm function). Fertilization and cleavage rates using husband's spermatozoa were significantly reduced in endometriosis couples (56%, n = 194, P < 0.001) and further significantly reduced in couples with unexplained infertility (52%, n = 327, P < 0.001) compared with tubal infertility (60%, n = 509). Using donor spermatozoa the rates were the same as using husband's spermatozoa in tubal infertility (61%, n = 27) or endometriosis (55%, n = 21) but significantly though only partly improved with unexplained infertility (57%, n = 60, P < 0.02). In unexplained infertility, a significantly increased proportion of couples experienced complete failure of fertilization and cleavage in a cycle (5-6% versus 2-3%). However, complete failure was not usually repetitive, and the affected couples did not account for the overall reduction in fertilization and cleavage rates, which remained significantly lower in the rest of the unexplained and endometriosis groups. Implantation and pregnancy rates appeared similar in all groups. The benefit of IVF treatment in cases of minor endometriosis and prolonged unexplained infertility is due to superabundance of oocytes obtained by stimulation. The reduction in natural fertility associated with endometriosis appears to be at least partly due to a reduced fertilizing ability of the oocyte. In unexplained infertility, there is distinct impairment due to otherwise unsuspected sperm dysfunction but probably also oocyte dysfunction.

Adult↗