Lower Probability Of Pregnancy Research Articles

Sperm mitochondrial DNA biomarkers and couple fecundity.

Do sperm mitochondrial DNA measures predict probability of pregnancy among couples in the general population? Those with high sperm mitochondrial DNA copy number (mtDNAcn) had as much as 50% lower odds of cycle-specific pregnancy, and 18% lower probability of pregnancy within 12 months. Semen parameters have been found to poorly predict reproductive success yet are the most prevalent diagnostic tool for male infertility. Increased sperm mtDNAcn and mitochondrial DNA deletions (mtDNAdel) have been associated with decreased semen quality and lower odds of fertilization in men seeking fertility treatment. A population-based prospective cohort study of couples discontinuing contraception to become pregnant recruited from 16 US counties from 2005 to 2009 followed for up to 16 months. Sperm mtDNAcn and mtDNAdel from 384 semen samples were assessed via triplex probe-based quantitative PCR. Probability of pregnancy within 1 year was compared by mitochondrial DNA, and discrete-time proportional hazards models were used to evaluate the relations with time-to-pregnancy (TTP) with adjustment for covariates. Higher sperm mtDNAcn was associated with lower pregnancy probability within 12 months and longer TTP. In unadjusted comparisons by quartile (Q), those in Q4 had a pregnancy probability of 63.5% (95% CI: 53.1% to 73.1%) compared to 82.3% (95% CI: 73.2% to 89.9%) for Q1 (P = 0.002). Similar results were observed in survival analyses adjusting for covariates to estimate fecundability odds ratios (FORs) comparing mtDNAcn in quartiles. Relative to those in Q1 of mtDNAcn, FORs (95% CI) were for Q2 of 0.78 (0.52 to 1.16), Q3 of 0.65 (0.44 to 0.96) and Q4 of 0.55 (0.37 to 0.81), and this trend of decreasing fecundability with increasing mtDNAcn quartile was statistically significant (FOR per log mtDNAcn = 0.37; P < 0.001). Sperm mtDNAdel was not associated with TTP. This prospective cohort study consisted primarily of Caucasian men and women and thus large diverse cohorts are necessary to confirm the associations between sperm mtDNAcn and couple pregnancy success in other races/ethnicities. Our results demonstrate that sperm mtDNAcn has utility as a biomarker of male reproductive health and probability of pregnancy success in the general population. This work was funded in part by the National Institute of Environmental Health Sciences, National Institutes of Health (R01-ES028298; PI: J.R.P.) and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contracts N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). The authors declare no competing interests. N/A.

Associations Between Preconception Plasma Fatty Acids and Pregnancy Outcomes.

Although fatty acids are involved in critical reproductive processes, the relationship between specific fatty acids and fertility is uncertain. We investigated the relationship between preconception plasma fatty acids and pregnancy outcomes. We included 1,228 women attempting pregnancy with one to two previous pregnancy losses from the EAGeR trial (2007-2011). Plasma fatty acids were measured at baseline. We used log-binomial regression to assess associations between fatty acids and pregnancy, pregnancy loss, and live birth, adjusting for age, race, smoking, BMI, physical activity, income, parity, treatment arm, and cholesterol. Although total saturated fatty acids (SFAs) were not associated with pregnancy outcomes, 14:0 (myristic acid; relative risk [RR] = 1.10, 95% confidence interval [CI] = 1.02, 1.19, per 0.1% increase) and 20:0 (arachidic acid; RR = 1.05, 95% CI = 1.01, 1.08, per 0.1% increase) were positively associated with live birth. Findings suggested a positive association between total monounsaturated fatty acids (MUFAs) and pregnancy and live birth and an inverse association with loss. Total polyunsaturated fatty acids (PUFAs) were associated with lower probability of pregnancy (RR = 0.97, 95% CI = 0.95, 1.00) and live birth (RR = 0.96, 95% CI = 0.94, 0.99), and increased risk of loss (RR = 1.10, 95% CI = 1.00, 1.20), per 1% increase. Trans fatty acids and n-3 fatty acids were not associated with pregnancy outcomes. Preconception total plasma MUFAs were positively associated with pregnancy and live birth. PUFAs were inversely associated with pregnancy outcomes. Specific SFAs were associated with a higher probability of live birth. Our results suggest that fatty acids may influence pregnancy outcomes.

Sperm selection with density gradient centrifugation and swim up: effect on DNA fragmentation in viable spermatozoa

Subjects increasing sperm DNA fragmentation (sDF) during Density Gradient Centrifugation (DGC), a common sperm selection procedure in Assisted Reproduction Techniques (ARTs), experience a 50% lower probability of pregnancy. Hence, identification of these subjects is of clinical importance. Here, we investigated whether such subjects are identified with higher accuracy detecting DNA fragmentation in viable (viable sDF) instead of total spermatozoa (total sDF) and whether swim up, an alternative procedure to DGC, does not increase sDF. With DGC, we identified 10/20 subjects increasing total sDF, and 2 more subjects using viable sDF. With swim up, we identified 8/40 subjects increasing total sDF, and 8 more subjects using viable sDF. In addition, viable sDF reveals more accurately the increase of the damage when it occurs. Finally, a multivariate analysis demonstrated that the proportional increase of sDF was higher after DGC respect to swim up. In conclusion, viable sDF is a more accurate parameter to reveal the increase of the damage by selection both with swim up and DGC. Swim up increases sDF in some samples, although at a lesser extent than DGC, suggesting that it should be used to select spermatozoa for ARTs when possible.

Association Between Pesticide Residue Intake From Consumption of Fruits and Vegetables and Pregnancy Outcomes Among Women Undergoing Infertility Treatment With Assisted Reproductive Technology

Animal experiments suggest that ingestion of pesticide mixtures at environmentally relevant concentrations decreases the number of live-born offspring. Whether the same is true in humans is unknown. To examine the association of preconception intake of pesticide residues in fruits and vegetables (FVs) with outcomes of infertility treatment with assisted reproductive technologies (ART). This analysis included 325 women who completed a diet assessment and subsequently underwent 541 ART cycles in the Environment and Reproductive Health (EARTH) prospective cohort study (2007-2016) at a fertility center at a teaching hospital. We categorized FVs as having high or low pesticide residues using a validated method based on surveillance data from the US Department of Agriculture. Cluster-weighted generalized estimating equations were used to analyze associations of high- and low-pesticide residue FV intake with ART outcomes. Adjusted probabilities of clinical pregnancy and live birth per treatment cycle. In the 325 participants (mean [SD] age, 35.1 [4.0] y; body mass index, 24.1 [4.3]), mean (SD) intakes of high- and low-pesticide residue FVs were 1.7 (1.0) and 2.8 (1.6) servings/d, respectively. Greater intake of high-pesticide residue FVs was associated with a lower probability of clinical pregnancy and live birth. Compared with women in the lowest quartile of high-pesticide FV intake (<1.0 servings/d), women in the highest quartile (≥2.3 servings/d) had 18% (95% CI, 5%-30%) lower probability of clinical pregnancy and 26% (95% CI, 13%-37%) lower probability of live birth. Intake of low-pesticide residue FVs was not significantly related to ART outcomes. Higher consumption of high-pesticide residue FVs was associated with lower probabilities of pregnancy and live birth following infertility treatment with ART. These data suggest that dietary pesticide exposure within the range of typical human exposure may be associated with adverse reproductive consequences.

Biomarkers of ovarian reserve as predictors of infertility

Diminished ovarian reserve (DOR), as determined by low antimüllerian hormone (AMH) and high, early follicular phase follicle stimulating hormone (FSH) levels in serum, have been associated with earlier menopause and low egg yield in response to ovarian stimulation. Some studies suggest women with DOR have a lower probability of pregnancy after assisted reproductive technology. Thus, it is presumed that DOR is a cause of infertility. We sought to determine if measures of ovarian reserve would be significantly associated with infertility.

Variation of DNA Fragmentation Levels During Density Gradient Sperm Selection for Assisted Reproduction Techniques: A Possible New Male Predictive Parameter of Pregnancy?

Predicting the outcome of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) is one main goal of the present research on assisted reproduction. To understand whether density gradient centrifugation (DGC), used to select sperm, can affect sperm DNA integrity and impact pregnancy rate (PR), we prospectively evaluated sperm DNA fragmentation (sDF) by TUNEL/PI, before and after DGC. sDF was studied in a cohort of 90 infertile couples the same day of IVF/ICSI treatment. After DGC, sDF increased in 41 samples (Group A, median sDF value: 29.25% [interquartile range, IQR: 16.01–41.63] in pre- and 60.40% [IQR: 32.92–93.53] in post-DGC) and decreased in 49 (Group B, median sDF value: 18.84% [IQR: 13.70–35.47] in pre- and 8.98% [IQR: 6.24–15.58] in post-DGC). PR was 17.1% and 34.4% in Group A and B, respectively (odds ratio [OR]: 2.58, 95% confidence interval [CI]: 0.95–7.04, P = 0.056). After adjustment for female factor, female and male age and female BMI, the estimated OR increased to 3.12 (95% CI: 1.05–9.27, P = 0.041). According to the subgroup analysis for presence/absence of female factor, heterogeneity in the association between the Group A and B and PR emerged (OR: 4.22, 95% CI: 1.16–15.30 and OR: 1.53, 95% CI: 0.23–10.40, respectively, for couples without, n = 59, and with, n = 31, female factor).This study provides the first evidence that the DGC procedure produces an increase in sDF in about half of the subjects undergoing IVF/ICSI, who then show a much lower probability of pregnancy, raising concerns about the safety of this selection procedure. Evaluation of sDF before and after DGC configures as a possible new prognostic parameter of pregnancy outcome in IVF/ICSI. Alternative sperm selection strategies are recommended for those subjects who undergo the damage after DGC.

The endometrium in assisted reproductive technology: How thin is thin?

A thin endometrium is encountered infrequently (2.4%) in assisted reproductive technology cycles. When it does occur it is a cause of concern as it is associated with lower implantation rate and pregnancy rate. Though pregnancies have been reported at 4 and 5 mm it is apparent that an endometrial thickness <6 mm is associated with a trend toward lower probability of pregnancy. Hormone replacement therapy – frozen embryo transfer (FET) cycles appear to give better results due to an improvement in endometrial receptivity (ER). The etiology of thin endometrium plays a significant part in its receptivity. A number of treatments have been tried to improve endometrial growth, but none has been validated so far. Confirming ER of a thin endometrium by an ER array test before FET offers reassurance.

Minimum inhibitory concentrations of selected antimicrobials against Escherichia coli and Trueperella pyogenes of bovine uterine origin

Minimum inhibitory concentrations (MIC) of 9 antimicrobials for isolates of 2 common bovine intrauterine bacterial pathogens, Escherichia coli (n=209) and Trueperella pyogenes (n=35), were determined using broth microdilution methodology. The isolates were recovered from dairy cows from 7 herds postpartum using the cytobrush technique. The pathogens were initially identified using phenotypic techniques. Additionally, PCR was used to confirm the identity of T. pyogenes isolates and to categorize the E. coli isolates into phylogenetic groups A, B1, B2, and D. Minimum inhibitory concentrations in excess of published cut-points or bimodal distributions of MIC indicated potential antimicrobial resistance to ampicillin, cefuroxime, cephapirin, and oxytetracycline for E. coli, and to oxytetracycline for T. pyogenes. Of the antimicrobials tested, ticarcillin/clavulanic acid, ceftiofur, and enrofloxacin had the lowest MIC for these 2 pathogens. Differences in MIC of some antimicrobials were found between herds, age, breeds, and E. coli phylogenetic groups. Isolation of E. coli with an MIC ≥8μg/mL of oxytetracycline at 23d postpartum was associated with a lower probability of pregnancy within 6wk of commencement of breeding compared with those isolates with an MIC <8μg/mL (relative risk=0.66). Minimum inhibitory concentrations for uterine pathogens were determined for isolates from New Zealand dairy cows. However, in the absence of either epidemiological or clinical interpretive criteria, the interpretation of these MIC remains unclear. Further studies are required to define interpretative criteria, including determination of pharmacokinetic and pharmacodynamic profiles for antimicrobials.

Impact of obesity on the results of fertility-sparing management for atypical hyperplasia and grade 1 endometrial cancer

ObjectivesThe aim of the present study was to evaluate the impact of obesity on reproductive and oncologic outcomes on the success of fertility-sparing management. MethodsThis retrospective multicenter cohort study included women treated conservatively for atypical hyperplasia (AH) and endometrial cancer (EC) to preserve fertility. Five inclusion criteria were defined: (i) the presence of AH or grade 1 EC confirmed by two pathologists; (ii) adequate radiological examination before conservative management; (iii) available body mass index (BMI) at the beginning of treatment; and (iv) a minimum follow-up time of six months. ResultsForty patients fulfilled the inclusion criteria (17 had EC, and 23 had AH), mean age and BMI were 33years and 29kg/m2 respectively. Among the 15 obese patients, after medical treatment, 10 patients responded (67%) and three relapsed, whereas in the 25 non-obese patients, 19 responded (76%) and three relapsed (p=0.72). The overall pregnancy rate and follow-up time were 35% and 35months respectively. Among the 15 obese patients, after medical treatment, two patients became pregnant, whereas in the 25 non-obese patients, 12 became pregnant (p=0.04). ConclusionDespite similar response and recurrence rates, our results suggest that fertility-sparing management for AH and EC is associated with a lower probability of pregnancy in obese patients.

Associations between decreased fertility and management factors, claw health, and somatic cell count in Swedish dairy cows

The aim of this retrospective single-cohort study was to investigate if a rapid change in feeding, management, or housing or an increasing incidence of claw diseases or udder health problems is associated with decreased reproductive performance. Data on individual cows and herds were retrieved from the Swedish official milk recording system and questionnaire data on feeding system was obtained from the regional dairy associations. In total, 63,561 cows in 759 herds were included in the study. The associations between the probability of pregnancy at first insemination and number of inseminations per animal submitted for artificial insemination and potential predictor variables were investigated using a logistic regression model and a Poisson regression model, respectively. The results indicated that cows with severe claw lesions or an increasing somatic cell count after calving had a lower probability of pregnancy at first insemination and had a higher number of inseminations per animal submitted for artificial insemination than healthy cows. Variables representing a change in housing, production system, or milking system within the period from 6mo before calving until establishment of a new pregnancy were significantly associated with decreased reproductive performance. No differences in fertility were observed between cows milked in an automatic milking system compared with cows milked conventionally. The results indicate that a change of system, rather than the actual type of milking or housing system negatively affects reproductive performance. Special attention should therefore be paid to the fertility of cows when the herd management is changing. It is also important to prevent claw lesions and increasing cell counts after calving to avoid a decrease in reproductive performance.

High exposure to progesterone between the end of menstruation and the day of triggering final oocyte maturation is associated with a decreased probability of pregnancy in patients treated by in vitro fertilization and intracytoplasmic sperm injection

To investigate the association between the probability of pregnancy and hormone exposure between the end of menstruation and the day of triggering final oocyte maturation (menstruation-free interval). Prospective study. University. One hundred women (aged ≤ 39 years) stimulated with a fixed dose of recombinant follicle-stimulating hormone (200 IU). Daily gonadotropin-releasing hormone antagonist (GnRH, 0.25 mg) used from day 6 of stimulation onward, final oocyte maturation triggered by administration of 10,000 IU of human chorionic gonadotropin (hCG) as soon as ≥ 3 follicles ≥ 17 mm were present, and hormone assessment performed at initiation of stimulation, on the first day after menstruation had stopped, on the day of antagonist initiation, and on the day of hCG administration. The association between hormone exposure during the menstruation-free interval and the probability of ongoing pregnancy. The exposure to progesterone during the menstruation-free interval was statistically significantly higher in patients who did not become pregnant compared with those who did (4.20 ± 2.54 vs. 3.13 ± 1.14, respectively). Binary logistic regression confirmed the adverse effect of the increased exposure to progesterone for the achievement of pregnancy. In recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in vitro fertilization/intracytoplasmic sperm injection cycles, a lower probability of pregnancy is associated with a higher exposure to progesterone during the menstruation-free interval.

GnRH antagonists in ovarian stimulation for IVF

The present review describes, on the basis of the currently available evidence, the consensus reached by a group of experts on the use of gonadotropin-releasing hormone (GnRH) antagonists in ovarian stimulation for IVF. The single or multiple low-dose administration of GnRH antagonist during the late-follicular phase effectively prevents a premature rise in serum luteinizing hormone (LH) levels in most women. Although controversy remains, most comparative studies suggest a slight, not significant reduction in the probability of pregnancy after IVF using GnRH antagonist versus GnRH agonist co-treatment. Published meta-analyses suggest that this slight difference in pregnancy rates is not attributed to chance. Further studies applying varying treatment regimens and outcome measures are required. Data are not in favour of a need to modify the starting dose of gonadotropins. Data are not in favour of increasing gonadotropin dose at GnRH antagonist initiation. The addition of LH from the initiation of ovarian stimulation or from GnRH antagonist administration does not appear to be necessary. Replacement of human chorionic gonadotropin (HCG) by GnRH agonist for triggering final oocyte maturation is associated with a lower probability of pregnancy. The optimal timing for HCG administration needs to be explored further. GnRH antagonist initiation on day 6 of stimulation appears to be superior to flexible initiation by a follicle of 14-16 mm, although earlier GnRH antagonist administration is worth further evaluation. Luteal phase supplementation in GnRH antagonist protocols remains mandatory in IVF. Effects of GnRH antagonist co-treatment on the incidence of ovarian hyperstimulation syndrome remains uncertain, although a trend is present in favour of the GnRH antagonists. The role of GnRH antagonists in ovarian stimulation for IVF appears to be promising, although many questions regarding preferred dose regimens and effects on clinical outcomes remain.

Factors potentially affecting fertility of lactating dairy cow recipients

Objectives of this study were to evaluate factors that could affect pregnancy rate after embryo transfer (ET) in lactating dairy cow recipients. The trial was conducted at a dairy farm located in Descalvado, SP, Brazil from October 2003 to September 2004. From 1037 cows with CL that were treated with an injection of PGF 2α, 43.3% were detected in heat; 263 were previously assigned at day of PGF 2α injection for AI and 186 for ET. Ovulation rate was 85.7% (385/449). Pregnancy rate for cows with CL for AI and embryo transfer recipients were 36.5% (84/230) and 58.7% (91/155) at day 25 and 33.0% (76/230) and 45.8% (71/155) at day 46, respectively. Embryonic loss were 9.5% (8/84) for the AI group and 21.9% (20/91) for the ET group. Average milk production was 31.4 L/day/cow. Average daily milk production from 7 days before PGF 2α injection to 7 days after ET tended ( P < 0.10) to influence pregnancy rate on days 25 and 46. Average daily milk production from the day of embryo transfer to 7 days after influenced embryonic loss ( P < 0.05). Cows with higher milk production had lower probability of pregnancy and higher probability of embryonic loss. Cows with higher days in milk had higher probability of pregnancy. Cows with higher rectal body temperature had lower probability of pregnancy and higher probability of embryonic loss. The influence of high milk yield and body temperature on fertility in lactating dairy cow recipients suggests that these effects can occur also after embryo reaches the blastocyst stage.

Resynchrony of postpartum dairy cows previously treated for anestrus

Cows that are diagnosed as anestrus (defined as >3 weeks postpartum, not detected in estrus by 1 week before commencement of seasonal breeding and without a palpable corpus luteum) have a lower probability of being inseminated, a lower conception rate to insemination and hence a lower probability of pregnancy within the breeding period. A current progesterone (P) and estradiol benzoate (EB) treatment for anestrus results in an 85% insemination rate, but only 57% of cows not conceiving to that first insemination are subsequently detected in estrus 14–28 days later. Resynchrony after an initial anestrous treatment has been used to increase the probability that cows not conceiving to first insemination will subsequently be detected in estrus. Anestrous cows ( n=971) were initially treated with an intravaginal P-releasing device for 6 days and given 1 mg EB 1 day after device removal (day of EB treatment=Day 0). Cows detected in estrus between Days 0 and 3 were assigned randomly to be treated with reinsertion of a used P-releasing device for 8 days (commencing on Day 15), with 0.5 mg EB at reinsertion and again 1 day after removal (EB-RS), treatment as for EB-RS group but with substitution of 250 μg GnRH for EB at device reinsertion (GnRH-RS), or left as untreated controls (no-RS). Resynchrony treatments increased the proportion of non-pregnant cows detected in estrus from Days 14 to 28 compared to no-RS (79.1, 69.8, and 55.1% for EB-RS, GnRH-RS, and no-RS, respectively; P<0.05). Fewer cows were pregnant by Days 28 and 56 following GnRH-RS than EB-RS and no-RS. The final pregnancy rate was higher following EB-RS treatment than no-RS or GnRH-RS treatment (95.0, 88.3, and 88.6%; P<0.05). In conclusion, EB-RS enhanced reproductive performance of anestrous cows compared to no-RS.

A Comparison of the Breeding Performance of Yearling and 2-Year-Old Hereford Bulls

Fort Keogh Livestock and Range Research Laboratory, Miles City, single-sire breeding herd records provided 1,728 observations on the breeding performance of yearling and 2-yr-old novice Line 1 Hereford bulls. Breeding results from the joint performance of the male and female, with the female as the elementary unit of observation, formed a Bernoulli experiment, in which the female either was pregnant or was not pregnant. Thus, the measure of performance is the probability of pregnancy, the probability being conditional on certain factors (e.g., female traits, bull traits and herd characteristics). The Logit model, not subject to the shortcomings of a linear probability model, was utilized to compare the breeding performance of the yearling with the 2-yr-old novice bulls. The observed difference in herd pregnancy rate between yearling and 2-yr-old bulls was explained largely by a lower probability of pregnancy when the female was a yearling heifer in a predominately heifer herd exposed to a good gain ratio yearling bull, or the female was of any age in a mixed-age herd exposed to a medium gain ratio yearling bull. The breeding performance of 2-yr-old novice and good or excellent gain ratio yearling bulls assigned to mixed-age female breeding herds was not statistically different. Decreased breeding performance was found for 2-yr-old cows nursing a calf. However, this result was attributed to the cow, because no discernible difference in performance due to bull age or other traits was found.

Studies of sperm competition in two species of muroid rodents

1. In three experiments on the effects of mating order, wild-type male deer mice, Peromyscus maniculatus bairdi were tested in competition with brown recessive, wide-band agouti, and blonde mutant males. Females of the homozygous recessive genotype received two ejaculatory series from a male of each genotype; mating order was varied. There were no significant effects of mating order on litter composition. In a parallel experiment wild-type and albino male prairie voles, Microtus ochrogaster, mated for one ejaculation each with albino females. There was a significant advantage with respect to litter composition for the male ejaculating last. Together with data from other species, these results suggest that effects of mating order are highly species-specific and must be evaluated for each species before speculations are made regarding the effects of multiple matings. 2. Males of various genotypes differed with respect to differential fertilizing capacity. Wild-type male deer mice outcompeted both brown recessive and wideband agouti males. The combinations of blonde and wild-type deer mice and albino and wild-type prairie voles yielded strain differences in litter composition in one mating order but not in the other. Counts of the numbers of sperm from males of different genotypes in the uteri of females revealed no sigificant strain differences. Thus, strain differences are not simply a function of sperm numbers. 3. Female deer mice mated or exposed to more than one male had a lower probability of pregnancy than those mated for comparable numbers of ejaculations with one male in previous studies. Additional data on pregnancy initiation in females of the brown-recessive genotype mated with one male revealed them to be only slightly less likely to become pregnant than wild-type females. Strain of male had little effect. 4. No significant effects on litter composition were attributable to the length of the delay between matings by successive males. This was established both via correlational analyses of the data from the mating order studies and in an additional experiment in deer mice in which delays of 2 h were imposed between the last ejaculation by the first male and introduction of a second male. 5. Litter composition in deer mice reflects the number of ejaculations attained by each of two males. In one experiment, female deer mice mated first with a blonde male and then with a wild-type male. The blonde male delivered three ejaculations and the wild-type male one ejaculation in one condition and the wild-type male three ejaculations and the blonde male one in the other. Litter composition was significantly affected.