Biological aging and the etiology of aneuploidy

A prevalent hypothesis concerning the cause of the rise in aneuploid conceptions with maternal age is that the changes that accompany normal ovarian aging increase the rate of meiotic errors in the oocyte. Biological aging of the ovary is accompanied by a decline in both the total oocyte pool and the number of antral follicles maturing per cycle, as well as changes in the levels of circulating reproductive hormones. The biological aging hypothesis predicts that aneuploidy rates should be higher in women with a prematurely reduced oocyte pool, and that women with trisomic conceptions should show signs of earlier ovarian aging than women of the same chronological age without trisomic conceptions. Comprehensive studies of aneuploidy in groups of women with known causes of premature ovarian failure remain to be done, though anecdotal evidence does suggest increased rates of pregnancy loss and aneuploidy. Smoking, which is a well-documented cause of earlier ovarian aging, is not associated with an increase in aneuploid conceptions. Evidence from women with unilateral ovariectomies is inconsistent. Support for the biological aging hypothesis was provided by one study showing that menopause occurred about a year earlier in women with a trisomic spontaneous abortion compared to women with chromosomally normal conceptions. Associations between high FSH and pregnancies with Down syndrome and chromosomally abnormal spontaneous abortions have also been reported. However, the most direct test of the hypothesis, which compared antral follicle counts and hormonal levels in women with trisomic pregnancies and those with chromosomally normal pregnancies, failed to find a difference in the expected direction. A prospective study of FSH levels in women with subfertility also failed to find an association with the rate of pregnancy loss. The bulk of evidence thus suggests that, if the processes of biological aging are indeed related to aneuploidy, they probably involve factors other than those measured by oocyte or antral follicle pool size and reproductive hormone levels.     

Maternal age-specific rates of numerical chromosome abnormalities with special reference to trisomy

Summary The effect of maternal age on the incidence of chromosomally normal spontaneous abortion and different categories of chromosome abnormality among all clinically recognized human pregnancies was evaluated. The results provide no evidence for a significant association of age with sex chromosome monosomy or polyploidy, but clearly demonstrate an effect of age on the frequency of trisomy and chromosomally normal spontaneous abortions. Estimated maternal age-specific rates of trisomy among all recognized pregnancies were calculated and suggest that a majority of oocytes of women aged 40 years and older may be aneuploid.     

Does the karyotype of a spontaneous abortion predict the karyotype of a subsequent abortion? Evidence from 273 women with two karyotyped spontaneous abortions.

At least two spontaneous abortions were karyotyped in 273 women during cytogenetic surveys in New York City and Honolulu. These pairs were analyzed using maximum-likelihood logistic-regression analysis to adjust for maternal age and location. There was a significantly increased risk for a chromosomally normal spontaneous abortion after a previous abortion with a normal karyotype. There was no increased risk for trisomy in a second spontaneous abortion following either a previous trisomic abortion or an abortion with another abnormal karyotype. This is unexpected, given the increased risk for trisomy found among live births and at prenatal diagnosis in young women with a previous trisomic birth. The most likely explanation is that the increased recurrence risk for trisomy is restricted to trisomy for only one or a few chromosomes, for reasons such as parental trisomy mosaicism. These data predict no increased risk of chromosome abnormality in future pregnancies after either (1) spontaneous abortions with trisomies of a kind that are always lethal in utero or (2) multiple early abortions in the presence of normal parental karyotypes.     

Skewed X-chromosome inactivation is associated with trisomy in women ascertained on the basis of recurrent spontaneous abortion or chromosomally abnormal pregnancies

An increase in extremely skewed X-chromosome inactivation (XCI) (> or = 90%) among women who experienced recurrent spontaneous abortion (RSA) has been previously reported. To further delineate the etiology of this association, we have evaluated XCI status in 207 women who experience RSA. A significant excess of trisomic losses was observed among the women who had RSA with skewed XCI versus those without skewed XCI (P=.02). There was also a significant excess of boys among live births in this group (P=.04), which is contrary to expectations if the cause of skewed XCI was only that these women carried X-linked lethal mutations. To confirm the association between skewed XCI and the risk of trisomy, an independent group of 53 women, ascertained on the basis of a prenatal diagnosis of trisomy mosaicism, were investigated. Only cases for which the trisomy was shown to be of maternal meiotic origin were included. The results show a significantly higher level of extreme skewing (> or = 90%) in women whose pregnancies involved placental trisomy mosaicism (17%) than in either of two separate control populations (n=102 and 99) (P=.02 compared with total control subjects). An additional 11 cases were ascertained on the basis of one or more trisomic-pregnancy losses. When all women in the present study with a trisomic pregnancy (n=103) were considered together, skewed XCI was identified in 18%, as compared with 7% in all controls (n=201) (P=.005). This difference was more pronounced when a cutoff of extreme skewing of 95% was used (10% vs. 1.5% skewed; P=.002). Maternal age was not associated with skewing in either the patient or control populations and therefore cannot account for the association with trisomy. Previous studies have shown that a reduced ovarian reserve is associated with increased risk of trisomic pregnancies. We hypothesize that the association between skewed XCI and trisomic pregnancies is produced by a common mechanism that underlies both and that involves a reduction of the size of the follicular pool.     

Skewed X Chromosome Inactivation and Trisomic Spontaneous Abortion: No Association

Several studies suggest that highly skewed X chromosome inactivation (HSXI) is associated with recurrent spontaneous abortion. We hypothesized that this association reflects an increased rate of trisomic conceptions due to anomalies on the X chromosome that lead both to HSXI and to a diminished oocyte pool. We compared the distribution of X chromosome inactivation (XCI) skewing percentages (range: 50%–100%) among women with spontaneous abortions in four karyotype groups—trisomy (n = 154), chromosomally normal male (n = 43), chromosomally normal female (n = 38), nontrisomic chromosomally abnormal (n = 61)—to the distribution for age-matched controls with chromosomally normal births (n = 388). In secondary analyses, we subdivided the nontrisomic chromosomally abnormal group, divided trisomies by chromosome, and classified women by reproductive history. Our data support neither an association of HSXI with all trisomies nor an association of HSXI with chromosomally normal male spontaneous abortions. We also find no association between HSXI and recurrent abortion (n = 45).     

A trisomic germ cell line and precocious chromatid segregation leads to recurrent trisomy 21 conception

A chromosomally normal 37-year-old woman was referred for preimplantation genetic diagnosis after having several conceptuses with trisomy 21. Segregation of chromosome 21 was assessed in unfertilised meiosis II oocytes and preimplantation embryos from PGD cycles using fluorescent in situ hybridisation (FISH). Of 7 preimplantation embryos, 5 were chromosomally abnormal with 4 having trisomy 21 and one being tetraploid. Of 4 oocytes, 3 had an abnormal chromosomal constitution with either an extra chromosome 21 or an extra chromatid 21. In one oocyte an extra chromatid 21 was detected in both the metaphase II complement and the first polar body providing the first direct evidence of a maternal trisomic germ cell line. Moreover, this result shows that the extra chromosome 21 can precociously divide into its two chromatids at the first meiotic division. Received: 9 September 1998 / Accepted: 26 November 1998     

A cytogenetic study of repeated spontaneous abortions.

During a cytogenetic study of spontaneous abortions, successive abortions from 40 couples were karyotyped. The chromosome constitutions of the first and second abortions were found to be highly correlated. In each of 21 instances in which the first abortion was chromosomally normal, the subsequent abortion(s) was normal as well. In nine cases, the two abortions were chromosomally abnormal, and in four of these, both abortions were trisomic. Combined with findings from other studies of consecutive spontaneous abortions, the present data indicate that certain couples are at an increased risk for either repeated chromosomally normal abortions or for repeated trisomic conceptions. The increased risk of trisomy does not seem to be restricted to a particular chromosome, and the magnitude of the risk increase appears to be independent of maternal age.     

Paternal age and trisomy among spontaneous abortions

Summary The relationship of paternal age to specific types of trisomy and to chromosomally normal loss was investigated in data drawn from a case-control study of spontaneous abortions. Differences in paternal age between karyotype groups and controls delivering after 28 weeks gestation were tested using an urn model analysis which adjusted, by regression, for maternal age and, by stratification, for the effects of design variables (payment status, phase of study) and demographic factors (language, ethnicity). The magnitude of paternal age differences was estimated using least squares regression analysis. For chromosomally normal cases there was no association with paternal age. Among the fourteen trisomy categories examined, four (7, 9, 18, 21) showed increased paternal age ( 1 year above expectation), three (13, 20, 22) showed decreased paternal age and the rest, including the most common, trisomy 16, showed negligible differences. Only the association with trisomy 22 was statistically significant (P = 0.012), with a predicted reduction in paternal age of 2.1 years (95% CI -4.9, -0.5 years). This association did not vary with maternal age, payment status, phase of study, language or ethnicity. Because previous observations are extensive, the relation of paternal age to trisomy 21 was examined further. The overall association was not significant ( = 0.8 years; 95% CI -0.8, 2.4 years). Moreover, there was evidence that the magnitude and direction of paternal age associations vary significantly within the sample, although not between subgroups defined on the basis of payment, phase of study, language or ethnicity. With respect to maternal age, the trend is towards a greater paternal age difference for trisomy 21 losses in younger women (P = 0.058). Given the number of tests performed, the finding for trisomy 22 and reduced paternal age could be due to chance. Among trisomy types, the direction of paternal age associations was not consistent for chromosomes grouped according to characteristics that might relate to the probability of nondisjunction, such as size, arm ratio, or nucleolar organizer region content, or to the potential viability of the trisomy. Thus, neither on statistical nor biological grounds do the data provide compelling evidence of paternal age effects on the trisomies found among spontaneous abortions, or on chromosomally normal losses.     

Sex ratio in normal and disomic sperm: evidence that the extra chromosome 21 preferentially segregates with the Y chromosome.

In humans, deviations from a 1:1 male:female ratio have been identified in both chromosomally normal and trisomic live births: among normal newborns there is a slight excess of males, among trisomy 18 live borns a large excess of females, and among trisomy 21 live borns an excess of males. These differences could arise from differential production of or fertilization by Y- or X-bearing sperm or from selection against male or female conceptions. To examine the proportion of Y- and X-bearing sperm in normal sperm and in sperm disomic for chromosomes 18 or 21, we used three-color FISH (to the X and Y and either chromosome 18 or chromosome 21) to analyze >300,000 sperm from 24 men. In apparently normal sperm, the sex ratio was nearly 1:1 (148,074 Y-bearing to 148,657 X-bearing sperm), and the value was not affected by the age of the donor. Certain of the donors, however, had significant excesses of Y- or X-bearing sperm. In disomy 18 sperm, there were virtually identical numbers of Y- and X-bearing sperm; thus, the excess of females in trisomy 18 presumably is due to selection against male trisomic conceptions. In contrast, we observed 69 Y-bearing and 44 X-bearing sperm disomic for chromosome 21. This is consistent with previous molecular studies, which have identified an excess of males among paternally derived cases of trisomy 21, and suggests that some of the excess of males among Down syndrome individuals is attributable to a nondisjunctional mechanism in which the extra chromosome 21 preferentially segregates with the Y chromosome.     

Uniparental disomy for chromosome 16 in humans.

The association between chromosomal mosaicism observed on chorionic villus sampling (CVS) and poor pregnancy outcome has been well documented. CVS mosaicism usually represents abnormal cell lines confined to the placenta and often involves chromosomal trisomy. Such confined placental mosaicism (CPM) may occur when there is complete dichotomy between a trisomic karyotype in the placenta and a normal diploid fetus or when both diploid and trisomic components are present within the placenta. Gestations involving pure or significant trisomy in placental lineages associated with a diploid fetal karyotype probably result from a trisomic zygote which has lost one copy of the trisomic chromosome in the embryonic progenitor cells during cleavage. Uniparental disomy would be expected to occur in one-third of such cases. Trisomy of chromosome 7, 9, 15, or 16 is most common among the gestations with these dichotomic CPMs. Nine pregnancies with trisomy 16 confined to the placenta were prenatally diagnosed. Pregnancy outcome, levels of trisomic cells in term placentas, and fetal uniparental disomy were studied. Intrauterine growth retardation (IUGR), low birthweight, or fetal death was observed in six of these pregnancies and correlated with high levels of trisomic cells in the term placentas. Four of the five cases of IUGR or fetal death showed fetal uniparental disomy for chromosome 16. One of the infants with maternal uniparental disomy 16 had a significant malformation (imperforate anus). All infants with normal intrauterine growth showed term placentas with low levels of trisomic cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Trisomy recurrence: a reconsideration based on North American data

Few reliable data exist concerning the recurrence risk for individual trisomies or the risk for recurrence of trisomy for a different chromosome. We collected records from two sources: (1) prenatal diagnoses performed at the Hopital Sainte-Justine in Montreal and (2) karyotype analyses performed at Genzyme. Using the standardized morbidity ratio (SMR), we compared the observed number of trisomies at prenatal diagnosis with the expected numbers, given maternal age-specific rates (by single year). SMRs were calculated both for recurrence of the same trisomy (homotrisomy) and of a different trisomy (heterotrisomy). After all cases with an index trisomy 21 were combined, the SMR for homotrisomy was 2.4 (90% CI 1.6-3.4; P=.0005). For women with both the index trisomy and subsequent prenatal diagnosis at age <30 years, the SMR was 8.0; it was 2.1 for women with both pregnancies at age >/=30 years. For the other index viable trisomies (13, 18, XXX, and XXY) combined, the SMR for homotrisomy was 2.5 (90% CI 0.7-8.0). For heterotrisomy, the SMR after an index trisomy 21 was 2.3 (90% CI 1.5-3.8, P=.0007); the SMR did not vary with maternal age at the first trisomy. When all cases with index viable trisomies were combined, the SMR for heterotrisomy was 1.6 (90% CI 1.1-2.4; P=.04). For prenatal diagnoses following a nonviable trisomy diagnosed in a spontaneous abortion (from Genzyme data only), the SMR for a viable trisomy was 1.8 (90% CI 1.1-3.0; P=.04). The significantly increased risk for heterotrisomy supports the hypothesis that some women have a risk for nondisjunction higher than do others of the same age.     

Effect of paternal age on the frequency of cytogenetic abnormalities in human spermatozoa

Many surveys have been performed to find etiological relationships between pregnancy outcome and specific risk factors, such as exposure to chemicals and radiation or parental age. Advanced maternal age is a strong risk factor for trisomic pregnancies, albeit there are considerable variations among the different chromosomes. The definite incidence of the various structural and numerical chromosome aberrations in spontaneous abortions and liveborns is well known, as well as the rate of maternally and paternally derived rearrangements. Nevertheless studies have failed to assert an age-dependent risk for men fathering chromosomally abnormal children. New techniques using fluorescence in situ hybridization render it possible to analyze spermatozoa directly for numerical and, to some extent, for structural aberrations. This article compiles the findings of studies on human spermatozoa over the last few years.     

Maternal smoking and trisomy among spontaneously aborted conceptions

In a study of spontaneous abortions, we found an apparently robust association of trisomy with smoking that varies with maternal age. Among women under age 30, smoking either before or at the time of conception is less common in women aborting trisomic conceptions than in controls delivering at 28 weeks or later. Among older women, smoking is more common in women aborting trisomic conceptions than in controls. Our results point to an effect of smoking on the frequency of trisomic abortions that varies with age, and they suggest that the causes of recognized trisomic abortions differ in younger and older women.     

Obstetric outcome in donor oocyte pregnancies: a matched-pair analysis

ABSTRACT: BACKGROUND: To investigate the obstetrical and perinatal impact of oocyte donation, a cohort of women who conceived after OD was compared with a matched control group of women who became pregnant through in vitro fertilisation with autologous oocytes (AO). METHODS: A matched-pair analysis has been performed at the Centre for Reproductive Medicine of the UZ Brussel, Dutch speaking Free University of Brussel. A total of 410 pregnancies resulted in birth beyond 20 weeks of gestation occurring over a period of 10 years, including 205 oocyte donation pregnancies and 205 ICSI pregnancies with autologous oocytes (AO). Patients in the OD group were matched on a one-to-one basis with the AO group in terms of age, ethnicity, parity and plurality. Matched groups were compared using paired t-tests for continuous variables and McNemar test for categorical variables. A conditional logistic regression analyses was performed adjusting for paternal age, age of the oocyte donor, number of embryos transferred, and singleton/twin pregnancy. RESULTS: Oocyte donation was associated with an increased risk of pregnancy induced hypertension (PIH) (matched OR: 1.502 CI: 1.024-2.204), and first trimester bleeding (matched OR: 1.493 CI: 1.036-2.15). No differences were observed between the two matched groups with regard to gestational age, mean birth weight and length, head circumference and Apgar scores. CONCLUSIONS: Oocyte donation is associated with an increased risk for PIH and first trimester bleeding independent of the recipients? age, parity and plurality, and independent of the age of the donor or the partner. However, oocyte donation has no impact on the overall perinatal outcome.     

Maternal age effect: the enigma of Down syndrome and other trisomic conditions.

Aneuploidy is the most frequently observed chromosome abnormality in human liveborn, abortuses and oocytes. The only etiological factor that has been established is advanced maternal age for the occurrence of trisomies, particularly trisomy 21 which causes Down syndrome. The maternal age effect remains an enigma. Recent molecular data bearing on this question are reviewed as are the hypotheses that have been proposed linking nondisjunction and maternal age. Rationale is presented for a compromised microcirculation hypothesis that explains the cause of nondisjunction and why its occurrence changes with maternal age from menarche to menopause. It takes into account two facts: (1) 95% of Down syndrome children receive their extra chromosome from their mother, and in 80% or more of these the nondisjunction occurred in the first meiotic division, which is completed in the ovary. (2) The ovarian follicle containing the primary oocyte has no internal circulation. The hypothesis proposes that aneuploid oocytes arise from a concatenation of events. It begins with hormonal imbalance that causes a less-than-optimal microvasculature to develop around the maturing and mature follicles. The resulting decrease in the size of the perifollicular capillary bed reduces the volume of blood flow through the area, leading to an oxygen deficit and a concomitant increase inside the follicle of carbon dioxide and anaerobic products, such as lactic acid. This in turn causes a decrease in the intracellular pH of the oocyte that diminishes the size of the spindle, with consequent displacement and nondisjunction of a chromosome. The compromised microcirculation hypothesis explains the occurrence of aneuploidy in primary and secondary oocytes, sperm precursor cells, tumor and embryonic cells. It also explains why women of all reproductive ages may have a Down syndrome child.     

Effect of hCG priming on embryonic development of immature oocytes collected from unstimulated women with polycystic ovarian syndrome

ABSTRACT: Backgroud: The effect of hCG priming on oocyte maturation and subsequently outcome in IVM cycles has remained a debated issue. A randomized controlled study was performed to investigate whether or not hCG priming prior to oocyte aspiration can improve the developmental competence of immature oocytes from unstimulated ovaries in women with polycystic ovarian syndrome (PCOS). MethodsEighty two patients with PCOS underwent IVM cycles. Each patient was randomly assigned to the hCG-primed (10,000 IU) or non-primed groups 36-38 hours before oocyte retrieval depending on the computerized random table. After the oocytes had in vitro matured, fertilizationculture and embryo transfer were performed. ResultsThe average number of cumulus-oocyte complexes (COCs) recovered was 13.80 and 14.35 in the hCG-primed and non-primed groups, respectively (p>0.05). The maturation rate of COCs was significantly improved in the hCG-primed group (55.43% vs. 42.29%; p<0.05). The fertilization and cleavage rates were comparable between the groups. The hCG-primed and non-primed groups did not differ with respect to the clinical pregnancy (37.50% vs. 50.00%), live birth (22.50% vs. 30.95%), and implantation rates (32.86% vs. 32.56%). The pregnancy losses was 6 (40.00%) of 15 clinical pregnancies in the hCG-primed groupand 8 (38.10%) of 21 clinical pregnancies in the non-primed group. CONCLUSIONS: While a significant improvement in the nuclear maturation rate of immature oocytes was observed in hCG-primed IVM cycles with PCOS patients, the use of hCG prior to oocyte retrieval did not improve the subsequent embryo developmental competence. The high rate of pregnancy loss in IVM cycles should receive more attention.     

Erythropoiesis in the fetal trisomy 19 mouse. I. Characterization of erythrocyte populations in peripheral blood

Changes in the type, size, and relative percentage of different erythrocyte populations in the peripheral blood of individual trisomy 19 and normal littermate mouse fetuses were studied from 12 gestational days to term. Large nucleated erythrocytes of yolk-sac origin comprise the first population of cells and are gradually diluted out of the circulation by nonnucleated erythrocytes of hepatic origin. This transition occurs between 12 and 16 gestational days. The rate of decline of the nucleated erythrocytes in the trisomic animals lagged by approximately 1 day behind the normal littermates, so that they did not completely disappear from the peripheral circulation until day 17. A slight decrease in size of the nonnucleated erythrocytes which occurs with increasing gestational age was also delayed by approximately 1 day in the trisomic fetuses. These observations are consistent with an hypothesis that one effect of the murine trisomy 19 genome is to retard by 1 day the growth and development of the affected animal.     

Effects of maternal age on oocyte developmental competence

The widespread use of a variety of assisted reproductive technologies has removed many of the constraints that previously restricted mammalian reproduction to the period between onset of puberty and reproductive senescence. In vitro embryo production systems now allow oocytes from very young animals to undergo fertilization and form embryos capable of development to normal offspring, albeit at somewhat reduced efficiencies compared to oocytes from adult females. They also can overcome infertility associated with advanced age of animals and women. This review examines oocyte developmental competence as the limiting factor in applications of assisted reproductive technologies for both juvenile and aged females. Age of oocyte donor is a significant factor influencing developmental competence of the oocyte. Age-related abnormalities of oocytes include a) meiotic incompetence or inability to complete meiotic maturation resulting in oocytes incapable of fertilization; b) errors in meiosis that can be compatible with fertilization but lead to genetic abnormalities that compromise embryo viability; and c) cytoplasmic deficiencies that are expressed at several stages of development before or after fertilization. In general, oocytes from juvenile donors and the embryos derived therefrom appear less robust and may be less tolerant to suboptimal handling and in vitro culture conditions than are adult oocytes. Research to identify specific cytoplasmic deficiencies of juvenile oocytes may enable modifications of culture conditions to correct such deficiencies and thus enhance developmental competence. Use of oocytes from aged donors for assisted reproduction can have a variety of applications such as extending the reproductive life of individual old females whose offspring still have high commercial value, and conservation of genetic resources such as rare breeds of livestock and endangered species. In general, female fertility decreases with advancing age. Studies of women in oocyte donation programs have established reduced oocyte competence as the major cause of declining fertility with age, although inadequate endometrial function can also be a contributing factor. Most research has emphasized the importance of chromosomal abnormalities because of the well established increase in aneuploidy with increasing maternal age but little is known about the underlying cellular and molecular mechanisms. Research aimed at identifying the specific developmental deficiencies of oocytes from juvenile donors and abnormalities of oocytes from aged females will assist in overcoming present bottlenecks that limit the efficiency of assisted reproduction technologies. Such research will also be crucial to the development of new oocyte-based technologies for overcoming infertility and possibly subverting chromosomal abnormalities in women approaching menopause.     

Q-banding of chromosomes in human spontaneous abortions

Chromosome studies of 242 spontaneous abortions were carried out by Q-banding technique. The abortuses were selected for study because they were phenotypically abnormal, had not progressed beyond 12 weeks development or were from women with repeated abortions. Chromosome anomalies were found in 126 (52%) of the abortuses. Of these, 71 (56%) were trisomies. Trisomies were found for all the autosomes except Nos. 1, 3, 5, 11, 17 and 18. Triploidy was the second commonest anomaly in this series, making up 26 (21%) of the total anomalies. About 70% of these had an XXY sex chromosome complement. Only 16 (13%) of the abortuses had X monosomy, a lower frequency than would be expected in an unselected study. Tetraploidy was found in 8 abortuses and the 5 remaining specimens had various anomalies. These included 3 translocations, a trisomy 21,X monosomy and a ring chromosome 13. Except for the greater frequency of XXY than XXX sex chromosomes in the triploids, there was no evidence of a distortion of the sex ratio, either among the trisomic or among the chromosomally normal abortuses.     

Ovum pick up, in vitro embryo production, and pregnancy rates from a large-scale commercial program using Nelore cattle (Bos indicus) donors

The objective was to clarify in vitro production of bovine embryos in Brazil. Data from 656 ovum pick-up/in vitro production (OPU/IVP) procedures, performed on 317 Nelore (Bos indicus) donors, without hormone stimulation or control of ovarian follicular waves, were analysed. Donors were subjected to OPU from one to nine times (no specific schedule), with < 15 d between consecutive procedures. There were 20,848 oocytes, of which 15,747 (75.53%) were considered viable, 5,446 embryos were obtained, 5,398 embryos were immediately transferred, resulting in 1,974 pregnancies (36.57%) at Day 30 and 1,788 (33.12%) pregnancies at Day 60. The average number of total and viable oocytes produced per OPU session was (mean ± SEM) 30.84 ± 0.88 and 23.35 ± 0.7 (average of 8.1 ± 0.3 embryos and 3.0 ± 0.1 pregnancies per OPU-IVP procedure). Since oocyte production varied widely among donor, they were designated as very high, high, intermediate, and low, with 58.94 ± 2.04, 32.61 ± 0.50, 22.13 ± 0.50, and 10.26 ± 0.57 oocytes, respectively, produced by 78, 80, 79, and 80 donors. The number of viable oocytes recovered ranged from 0 to 128; since donors with numerous viable oocytes produced many viable embryos and pregnancies, oocyte production was useful for donor selection. However, there was no significant effect of the number of OPU sessions per donor on mean numbers of oocytes produced. In conclusion, we confirmed field reports of high oocyte production by some Nelore donors and demonstrated individual variation in oocyte yield, which was associated with embryo production and pregnancy rates.