Effect of maternal age on the outcomes of in vitro fertilization and embryo transfer (IVF-ET)

This is a retrospective, observational study to evaluate the effect of maternal age on the outcomes of in vitro fertilization and embryo transfer (IVF-ET). 11830 IVF-ET cycles from 10268 women were included. Four groups of different maternal age periods were compared. The groups were 21?C30 years old group (4549 cycles), 31?C35 years old group (4424 cycles), 36?C40 years old group (2429 cycles), and over 40 years old group (428 cycles). The mean starting dose of Gn and mean total dose of Gn in each cycle were significantly higher (P<0.01), while the mean retrieved oocyte number was significantly lower (P<0.01) in groups of higher maternal age period than those in each of the lower groups. The biochemical pregnancy rate and the clinical pregnancy rate were significantly lower (P<0.01), while the miscarriage rate was significantly higher (P<0.01) in groups of higher maternal age period than those in the lower groups. No difference was found in two-pronuclear zygotes (2PN) rate and good quality embryo rate among different groups. Birth defect rate was also comparable in the born babies in different groups. In the group with patients?? age over 40 years old, the pregnancy rate was 26.87%, the clinical pregnancy rate was 19.39%, while the miscarriage rate after clinical pregnancy was 36.14%. To draw the conclusion, patients with higher maternal age had worse IVF outcomes. In women of fertile age, patients between 20 and 30 years old have the best IVF outcomes. Patients over 40 years old have poor IVF outcome and high miscarriage rate, which suggested the necessity of preimplantation genetic screening (PGS).     

Probing the Effect of Human Normal Sperm Morphology Rate on Cycle Outcomes and Assisted Reproductive Methods Selection

Sperm morphology is the best predictor of fertilization potential, and the critical predictive information for supporting assisted reproductive methods selection. Given its important predictive value and the declining reality of semen quality in recent years, the threshold of normal sperm morphology rate (NSMR) is being constantly corrected and controversial, from the 4^th edition (14%) to the 5^th version (4%). We retrospectively analyzed 4756 cases of infertility patients treated with conventional-IVF(c-IVF) or ICSI, which were divided into three groups according to NSMR: ≥14%, 4%–14% and <4%. Here, we demonstrate that, with decrease in NSMR(≥14%, 4%–14%, <4%), in the c-IVF group, the rate of fertilization, normal fertilization, high-quality embryo, multi-pregnancy and birth weight of twins gradually decreased significantly (P<0.05), while the miscarriage rate was significantly increased (p<0.01) and implantation rate, clinical pregnancy rate, ectopic pregnancy rate, preterm birth rate, live birth rate, sex ratio, and birth weight(Singleton) showed no significant change. In the ICSI group, with decrease in NSMR (≥14%, 4%–14%, <4%), high-quality embryo rate, multi-pregnancy rate and birth weight of twins were gradually decreased significantly (p<0.05), while other parameters had no significant difference. Considering the clinical assisted methods selection, in the NFMR ≥14% group, normal fertilization rate of c-IVF was significantly higher than the ICSI group (P<0.05), in the 4%–14% group, birth weight (twins) of c-IVF were significantly higher than the ICSI group, in the <4% group, miscarriage of IVF was significantly higher than the ICSI group. Therefore, we conclude that NSMR is positively related to embryo reproductive potential, and when NSMR<4% (5^th edition), ICSI should be considered first, while the NSMR≥4%, c-IVF assisted reproduction might be preferred.     

Reproductive health among married and unmarried mothers aged less than 18, 18–19, and 20–24 years in the United States, 2014–2019: A population-based cross-sectional study

BackgroundStudies in low- and middle-income regions suggest that child marriage (<18 years) is a risk factor for poor reproductive outcomes among women. However, in high-income-country contexts where childbearing before age 18 occurs predominantly outside marriage, it is unknown whether marriage is adversely associated with reproductive health among mothers below age 18. This study examined the joint associations of marriage and adolescent maternal age group (<18, 18–19, and 20–24 years) with reproductive, maternal, and infant health indicators in the United States.Methods and findingsBirth registrations with US resident mothers aged ≤24 years with complete information on marital status were drawn from the 2014 to 2019 Natality Public Use Files (n = 5,669,824). Odds ratios for the interaction between marital status and maternal age group were estimated using multivariable logistic regression, adjusting for covariates such as maternal race/ethnicity and nativity status, federal program participation, and paternal age. Marriage prevalence was 3.6%, 13.2%, and 34.1% among births to mothers aged <18, 18–19, and 20–24 years, respectively. Age gradients in the adjusted odds ratios (AORs) were present for most indicators, and many gradients differed by marital status. Among births to mothers aged <18 years, marriage was associated with greater adjusted odds of prior pregnancy termination (AOR 1.64, 95% CI 1.52–1.77, p < 0.001), repeat birth (AOR 2.84, 95% CI 2.68–3.00, p < 0.001), maternal smoking (AOR 1.24, 95% CI 1.15–1.35, p < 0.001), and infant morbidity (AOR 1.07, 95% CI 1.01–1.14, p = 0.03), but weaker or reverse associations existed among births to older mothers. For all maternal age groups, marriage was associated with lower adjusted odds of late or no prenatal care initiation, sexually transmitted infection, and no breastfeeding at hospital discharge, but these beneficial associations were weaker among births to mothers aged <18 and 18–19 years. Limitations of the study include its cross-sectional nature and lack of information on marriage timing relative to prior pregnancy events.ConclusionsMarriage among mothers below age 18 is associated with both adverse and favorable reproductive, maternal, and infant health indicators. Heterogeneity exists in the relationship between marriage and reproductive health across adolescent maternal age groups, suggesting girl child marriages must be examined separately from marriages at older ages.

In a population-based study, Andrée-Anne Fafard St-Germain and colleagues examine the joint associations of marriage and adolescent maternal age group (<18, 18-19, and 20-24 years) with reproductive, maternal, and infant health indicators in the United States.     

Prediction of Maternal Cytomegalovirus Serostatus in Early Pregnancy: A Retrospective Analysis in Western Europe

Background

Cytomegalovirus (CMV) is the most prevalent congenital viral infection and thus places an enormous disease burden on newborn infants. Seroprevalence of maternal antibodies to CMV due to CMV exposure prior to pregnancy is currently the most important protective factor against congenital CMV disease. The aim of this study was to identify potential predictors, and to develop and evaluate a risk-predicting model for the maternal CMV serostatus in early pregnancy.

Methods

Maternal and paternal background information, as well as maternal CMV serostatus in early pregnancy from 882 pregnant women were analyzed. Women were divided into two groups based on their CMV serostatus, and were compared using univariate analysis. To predict serostatus based on epidemiological baseline characteristics, a multiple logistic regression model was calculated using stepwise model selection. Sensitivity and specificity were analyzed using ROC curves. A nomogram based on the model was developed.

Results

646 women were CMV seropositive (73.2%), and 236 were seronegative (26.8%). The groups differed significantly with respect to maternal age (p = 0.006), gravidity (p<0.001), parity (p<0.001), use of assisted reproduction techniques (p = 0.018), maternal and paternal migration background (p<0.001), and maternal and paternal education level (p<0.001). ROC evaluation of the selected prediction model revealed an area under the curve of 0.83 (95%CI: 0.8–0.86), yielding sensitivity and specificity values of 0.69 and 0.86, respectively.

Conclusion

We identified predictors of maternal CMV serostatus in early pregnancy and developed a risk-predicting model based on baseline epidemiological characteristics. Our findings provide easy accessible information that can influence the counseling of pregnant woman in terms of their CMV-associated risk.     

Identifying Maternal Constraints on Fetal Growth and Subsequent Perinatal Outcomes Using a Multiple Embryo Implantation Model

IntroductionAlthough the majority of singleton births after in vitro fertilization (IVF) are uncomplicated, studies have suggested that IVF pregnancies may be independently associated with low birth weight (LBW), preterm birth (PTB), and perinatal mortality. These outcomes complicate multiple gestations as expected, but have also been reported in singletons. A multiple embryo implantation model allows for assessment of the early in utero environment, and therefore, assessment of any maternal constraints on developing fetuses. We question whether adverse perinatal outcomes associated with assisted reproductive techniques (ART) occur as a result of maternal physiologic adaptations.ResultsA total of 17,415 cycles were analyzed. The average maternal age was 36.9 (±5.0) years. An overall fertilization rate of 73.4% generated approximately 48,708 good quality cleavage-stage embryos. In most patients (92.8%), an average of 3 embryos were transferred. The clinical pregnancy rate was 39.2% (n = 6,281). The overall occurrence of multiple gestations was 38.2% (n = 2,608) consisting of 2,038 twin, 511 triplet, and 59 quadruplet pregnancies. Of these multiple gestations, 18.6% of twin, 54.2% of triplet and 76.3% of quadruplet gestations spontaneously reduced. Failure of the implanted embryo to progress was not related to maternal age. Singleton newborns resulting from multiple implantation sites had lower birth weights (P<0.01) and shorter gestational ages (P<0.01) than those from a single implanted embryo. The number of embryos transferred did not affect the gestational length of singleton newborns. Although the birth weights of singletons from multiple implantation sites (virtual singletons) were lower than true singletons, the birth weight of virtual singletons were comparable to the birth weights of true twin, triplet, and quadruplet live births. Multiple logistic regression revealed that virtual singletons were an independent risk factor for PTB (odds ratio: 4.55, 95% CI 2.23–9.29) and LBW (odds ratio: 3.61, 95% CI 1.78–7.32), even after controlling for the number of oocytes, stimulation protocol type, sperm source, total gonadotropins administered, age, embryo quality, and day of embryo transfer.ConclusionsOur study highlights that embryonic implantation sites during early gestation set the growth profile of each embryo, dictating later growth patterns. Specifically, spontaneous reduction of an embryo after multiple embryo implantations can confer greater perinatal risk in the form of LBW and PTB to the surviving fetus. Our findings suggest that maternal constraints or physiologic adaptations maybe one of the mechanisms mediating adverse perinatal outcomes when multiple embryo implantation occurs.     

Utilizing FMR1 Gene Mutations as Predictors of Treatment Success in Human In Vitro Fertilization

Context

Mutations of the fragile X mental retardation 1 (FMR1) gene are associated with distinct ovarian aging patterns.

Objective

To confirm in human in vitro fertilization (IVF) that FMR1 affects outcomes, and to determine whether this reflects differences in ovarian aging between FMR1 mutations, egg/embryo quality or an effect on implantation.

Design, Setting, Patients

IVF outcomes were investigated in a private infertility center in reference to patients'' FMR1 mutations based on a normal range of CGG_{n = 26–34} and sub-genotypes high (CGG_n>34) and low (CGG_<26). The study included 3 distinct sections and study populations: (i) A generalized mixed-effects model of morphology (777 embryos, 168 IVF cycles, 125 infertile women at all ages) investigated whether embryo quality is associated with FMR1; (ii) 1041 embryos in 149 IVF cycles in presumed fertile women assessed whether the FMR1 gene is associated with aneuploidy; (iii) 352 infertile patients (< age 38; in 1^st IVF cycles) and 179 donor-recipient cycles, assessed whether the FMR1 gene affects IVF pregnancy chances via oocyte/embryo quality or non-oocyte maternal factors.

Interventions

Standardized IVF protocols.

Main Outcome Measures

Morphologic embryo quality, ploidy and pregnancy rates.

Results

(i) Embryo morphology was reduced in presence of a low FMR1 allele (P = 0.032). In absence of a low allele, the odds ratio (OR) of chance of good (vs. fair/poor) embryos was 1.637. (ii) FMR1 was not associated with aneuploidy, though aneuploidy increased with female age. (iii) Recipient pregnancy rates were neither associated with donor age or donor FMR1. In absence of a low FMR1 allele, OR of clinical pregnancy (vs. chemical or no pregnancy) was 2.244 in middle-aged infertility patients.

Conclusions

A low FMR1 allele (CGG_<26) is associated with significantly poorer morphologic embryo quality and pregnancy chance. As women age, low FMR1 alleles affect IVF pregnancy chances by reducing egg/embryo quality by mechanisms other than embryo aneuploidy.     

Decreased Sperm Motility Retarded ICSI Fertilization Rate in Severe Oligozoospermia but Good-Quality Embryo Transfer Had Achieved the Prospective Clinical Outcomes

IntroductionSpermatozoa motility is the critical parameter to affect the treatment outcomes during assisted reproductive technologies (ART), but its reproductive capability remains a little informed in condition of severe male factor infertility. This retrospective cohort study aimed to evaluate the effects of reduced sperm motility on the embryological and clinical outcomes in intra-cytoplasmic sperm injection (ICSI) treatment of severe oligozoospermia.ResultsThe reduction in the number of motile sperm in four groups of severe oligozoospermia gave rise to comparable inability of the fertilization (p < 0.001) and a decreased rate of good-quality embryo at Day 3 (p < 0.001) by compared to the control. The cleavage rate of the derived zygotes was similar to the control. ET classes significantly affected the clinical outcomes (p < 0.001). Class I ET gave rise to similar rates of clinical outcomes between five groups, but Class II and Class III ET retarded the rates of pregnancy, implantation and live birth and this particularly occurred in Group C, D and E. The rate of early miscarriage was not comparably different between groups. Overall rates in all groups were 41.26% clinical pregnancy, 25.74% implantation and 36.32% live birth, which gave live birth to 252 girls and 252 boys.ConclusionsThe reduction of motile spermatozoa in severe oligozoospermia decreased the rates of fertilization and good-quality embryo. Obtaining and transfer of good-quality embryos was the good prognostic to achieve prospective clinical outcomes regardless of the severity of oligozoospermia.     

Effect of Paternal Age on Reproductive Outcomes of Intracytoplasmic Sperm Injection

The impact of paternal age on reproduction, especially using assisted reproductive technologies, has not been well studied to date. To investigate the effect of paternal age on reproductive outcomes, here we performed a retrospective analysis of 2,627 intracytoplasmic sperm injection (ICSI) cycles performed at the Reproductive Medicine Center of the Third Affiliated Hospital of Guangzhou Medical University (China) between January 2007 and May 2015. Effect of paternal age on embryo quality [number of fertilized oocytes, 2 pronucleus zygotes (2PNs), viable embryos, and high-quality embryos] was analyzed by multiple linear regression. Relationships between paternal age and pregnancy outcomes were analyzed by binary logistic regression. After adjusting for female age, no association between paternal age and the following parameters of embryo quality was observed: number of fertilized oocytes (B = -0.032; 95% CI -0.069–0.005; P = 0.088), number of 2PNs (B = -0.005; 95% CI -0.044–0.034; P = 0.806), and number of viable embryos (B = -0.025; 95% CI -0.052–0.001; P = 0.062). However, paternal age negatively influenced the number of high-quality embryos (B = -0.020; 95% CI -0.040–0.000; P = 0.045). Moreover, paternal age had no effect on pregnancy outcomes (OR for a 5-year interval), including the rates of clinical pregnancy (OR 0.919; 95% CI 0.839–1.006; P = 0.067), ongoing pregnancy (OR 0.914; 95% CI 0.833–1.003; P = 0.058), early pregnancy loss (OR 1.019; 95% CI 0.823–1.263; P = 0.861), live births (OR 0.916; 95% CI 0.833–1.007; P = 0.070), and preterm births (OR 1.061; 95% CI 0.898–1.254; P = 0.485). Therefore, increased paternal age negatively influences the number of high-quality embryos, but has no effect on pregnancy outcomes in couples undergoing ICSI cycles. However, more studies including men aged over 60 years with a longer-term follow-up are needed.     

The Influence of Single Nucleotide Polymorphism Microarray-Based Molecular Karyotype on Preimplantation Embryonic Development Potential

In order to investigate the influence of the molecular karyotype based on single nucleotide polymorphism (SNP) microarray on embryonic development potential in preimplantation genetic diagnosis (PGD), we retrospectively analyzed the clinical data generated by PGD using embryos retrieved from parents with chromosome rearrangements in our center. In total, 929 embryos from 119 couples had exact diagnosis and development status. The blastocyst formation rate of balanced molecular karyotype embryos was 56.6% (276/488), which was significantly higher than that of genetic imbalanced embryos 24.5% (108/441) (P<0.001). No significant difference was detected in blastocyst formation rates in the groups of maternal age<30, 30–35 and >35 respectively. Blastocyst formation rates of male and female embryos were 44.5% (183/411) and 38.8% (201/518) respectively, with no significant difference between them (P>0.05). The rates of balanced molecular karyotype embryos vary from groups of embryos with different cell numbers at 68 hours after insemination. The blastocyst formation rate of embryos with 6–8 cells (48.1%) was significantly higher than that of embryos with <6 cells (23.9%) and with >8 cells (42.9%) (P<0.05). As for the unbalanced embryos, there was no significant difference of the distribution of abnormal molecular karyotypes in the subgroup of the arrest, morula and blastocyst. Thus, we conclude that embryos with balanced molecular karyotype have significant higher development potential than those with imbalanced molecular karyotype whilst maternal age, embryo gender and types of abnormal molecular karyotype have no significant influence on blastocyst formation. Compared with embryos with <6 and >8 cells, embryos with 6–8 blastomeres have higher rate of balanced molecular karyotype and blastocyst formation.     

Focus: Rare Disease: Behçet’s Disease and Pregnancy: A Retrospective Case-control Study

Background: Behçet’s disease (BD) is a rare chronic multisystemic vasculitis of unknown etiology. It is usually diagnosed between the 2^nd and 4^th decades of life, so its association with pregnancy is not unusual. This study aims to characterize the evolution of pregnancy in a group of pregnant women with BD and the impact of this pathology in embryo-fetal morbidity. Methods: A retrospective case-control study included 49 pregnancies in women suffering from BD, followed in our institution. Pregnancy outcomes were compared with a control group of healthy pregnant women. Two controls per case were randomly selected. Statistical analysis used SPSS 25.0, and a p-value of 0.05 was considered statistically significant. Results: Forty-nine pregnancies were included in 27 patients with BD. BD exacerbation occurred in 32.6% of the pregnancies. There were no significant statistical differences between the two groups regarding the rate of preterm delivery, gestational diabetes, and preeclampsia (p>0.05). In the BD group, we found a higher rate of miscarriage (24.5%) and fetal growth restriction (FGR, 13.3%, p<0.05). In the study group, 13 (32.5%) of the pregnant patients did not need treatment. The cesarean rate was significantly higher in the BD group (43.2% vs 20.4% in the control group, p<0.05), and there were no significant differences in median gestational age at the time of delivery (p>0.05). The birth weight of newborns did not differ significantly between the groups. There was no association of BD with maternal morbidity and neonatal complications. Conclusion: In this study, the majority of pregnant with BD did not present clinical exacerbation of their pathology. However, BD may have an adverse influence on pregnancy outcomes. FGR and miscarriage rates were significantly higher in the study group.     

Risk of miscarriage in women with chronic diseases in Norway: A registry linkage study

BackgroundIncreased risk of miscarriage has been reported for women with specific chronic health conditions. A broader investigation of chronic diseases and miscarriage risk may uncover patterns across categories of illness. The objective of this study was to study the risk of miscarriage according to various preexisting chronic diseases.Methods and findingsWe conducted a registry-based study. Registered pregnancies (n = 593,009) in Norway between 2010 and 2016 were identified through 3 national health registries (birth register, general practitioner data, and patient registries). Six broad categories of illness were identified, comprising 25 chronic diseases defined by diagnostic codes used in general practitioner and patient registries. We required that the diseases were diagnosed before the pregnancy of interest. Miscarriage risk according to underlying chronic diseases was estimated as odds ratios (ORs) using generalized estimating equations adjusting for woman’s age. The mean age of women at the start of pregnancy was 29.7 years (SD 5.6 years). We observed an increased risk of miscarriage among women with cardiometabolic diseases (OR 1.25, 95% CI 1.20 to 1.31; p-value <0.001). Within this category, risks were elevated for all conditions: atherosclerosis (2.22; 1.42 to 3.49; p-value <0.001), hypertensive disorders (1.19; 1.13 to 1.26; p-value <0.001), and type 2 diabetes (1.38; 1.26 to 1.51; p-value <0.001). Among other categories of disease, risks were elevated for hypoparathyroidism (2.58; 1.35 to 4.92; p-value 0.004), Cushing syndrome (1.97; 1.06 to 3.65; p-value 0.03), Crohn’s disease (OR 1.31; 95% CI: 1.18 to 1.45; p-value 0.001), and endometriosis (1.22; 1.15 to 1.29; p-value <0.001). Findings were largely unchanged after mutual adjustment. Limitations of this study include our inability to adjust for measures of socioeconomic position or lifestyle characteristics, in addition to the rareness of some of the conditions providing limited power.ConclusionsIn this registry study, we found that, although risk of miscarriage was largely unaffected by maternal chronic diseases, risk of miscarriage was associated with conditions related to cardiometabolic health. This finding is consistent with emerging evidence linking cardiovascular risk factors to pregnancy complications.

In this registry data study, Maria Magnus and colleagues study associations between miscarriage risk and chronic conditions.     

T2 Values of Posterior Horns of Knee Menisci in Asymptomatic Subjects

Purpose

The magnetic resonance (MR) T2 value of cartilage is a reliable indicator of tissue properties and therefore may be used as an objective diagnostic tool in early meniscal degeneration. The purpose of this study was to investigate age, gender, location, and zonal differences in MR T2 value of the posterior horns of knee menisci in asymptomatic subjects.

Methods

Sixty asymptomatic volunteers (30 men and 30 women) were enrolled and divided into three different age groups: 20–34, 35–49 and 50–70 years. The inclusion criteria were BMI<30 kg/cm² _, normalized Western Ontario and McMaster Universities (WOMAC) pain score of zero, and no evidence of meniscal and ligamentous abnormalities on routine knee MR imaging. The T2 values were measured on images acquired with a T2-weighted fat-suppressed turbo spin-echo sequence at 3T.

Results

The mean T2 values in both medial and lateral menisci for the 20–34, 35–49, and 50–70 age groups were 9.94 msec±0.94, 10.73 msec±1.55, and 12.36 msec±2.27, respectively, for women and 9.17 msec±0.74, 9.64 msec±0.67, and 10.95 msec±1.33, respectively, for men. The T2 values were significantly higher in the 50–70 age group than the 20–34 age group (P<0.001) and in women than in men (P = 0.001, 0.004, and 0.049 for each respective age group). T2 values were significantly higher in medial menisci than in lateral menisci only in women age 50–70 (3.33 msec, P = 0.006) and in the white zone and red/white zone of the 50–70 and 35–49 age groups than that of the 20–34 age group (2.47, 1.02; 2.77, 1.16 msec, respectively, all P<0.01).

Conclusion

The MR T2 values of the posterior meniscal horns increase with increasing age in women and are higher in women than in men. The age-related rise of T2 values appears to be more severe in medial menisci than in lateral menisci. Differences exist in the white zone and red/white zone.     

Reduction of Maternal Mortality with Highly Active Antiretroviral Therapy in a Large Cohort of HIV-Infected Pregnant Women in Malawi and Mozambique

Background

HIV infection is a major contributor to maternal mortality in resource-limited settings. The Drug Resource Enhancement Against AIDS and Malnutrition Programme has been promoting HAART use during pregnancy and postpartum for Prevention-of-mother-to-child-HIV transmission (PMTCT) irrespective of maternal CD4 cell counts since 2002.

Methods

Records for all HIV+ pregnancies followed in Mozambique and Malawi from 6/2002 to 6/2010 were reviewed. The cohort was comprised by pregnancies where women were referred for PMTCT and started HAART during prenatal care (n = 8172, group 1) and pregnancies where women were referred on established HAART (n = 1978, group 2).

Results

10,150 pregnancies were followed. Median (IQR) baseline values were age 26 years (IQR:23–30), CD4 count 392 cells/mm³ (IQR:258–563), Viral Load log₁₀ 3.9 (IQR:3.2–4.4), BMI 23.4 (IQR:21.5–25.7), Hemoglobin 10.0 (IQR: 9.0–11.0). 101 maternal deaths (0.99%) occurred during pregnancy to 6 weeks postpartum: 87 (1.1%) in group 1 and 14 (0.7%) in group 2. Mortality was 1.3% in women with <than 350 CD4 cells/mm³ and 0.7% in women with greater than 350 CD4s cells/mm³ [OR = 1.9 (CL 1.3–2.9) p = 0.001]. Mortality was higher in patients with shorter antenatal HAART: 22/991 (2.2%) if less than 30 days and 79/9159 (0.9%) if 31 days or greater [OR = 2.6 (CL 1.6–4.2) p<0.001]. By multivariate analysis, shorter antenatal HAART (p<0.001), baseline values for CD4 cell count (p = 0.012), hemoglobin (p = 0.02), and BMI (p<0.001) were associated with mortality. Four years later, survival was 92% for women with shorter antenatal HAART and 98% for women on established therapy prior to pregnancy, p = 0.001.

Conclusions

Antiretrovirals for PMTCT purposes have significant impact on maternal mortality as do CD4 counts and nutritional status. In resource-limited settings, PMTCT programs should provide universal HAART to all HIV+ pregnant women given its impact in prevention of maternal death.     

Increasing Maternal Age Is Associated with Taller Stature and Reduced Abdominal Fat in Their Children

Background

Maternal age at childbirth continues to increase worldwide. We aimed to assess whether increasing maternal age is associated with changes in childhood height, body composition, and metabolism.

Methods

277 healthy pre-pubertal children, born 37–41 weeks gestation were studied. Assessments included: height and weight corrected for parental measurements, DEXA-derived body composition, fasting lipids, glucose, insulin, and hormonal profiles. Subjects were separated according to maternal age at childbirth: <30, 30–35, and >35 years.

Results

Our cohort consisted of 126 girls and 151 boys, aged 7.4±2.2 years (range 3–10); maternal age at childbirth was 33.3±4.7 years (range 19–44). Children of mothers aged >35 and 30–35 years at childbirth were taller than children of mothers aged <30 years by 0.26 (p = 0.002) and 0.23 (p = 0.042) SDS, respectively. There was a reduction in childhood BMISDS with increasing maternal age at childbirth, and children of mothers aged >35 years at childbirth were 0.61 SDS slimmer than those of mothers <30 years (p = 0.049). Children of mothers aged 30–35 (p = 0.022) and >35 (p = 0.036) years at childbirth had abdominal adiposity reduced by 10% and 13%, respectively, compared to those in the <30 group. Children of mothers aged 30–35 years at childbirth displayed a 19% increase in IGF-I concentrations compared to offspring in <30 group (p = 0.042). Conversely, IGF-II concentrations were lower among the children born to mothers aged 30–35 (6.5%; p = 0.004) and >35 (8.1%; p = 0.005) compared to those of mothers aged <30 years. Girls of mothers aged 30–35 years at childbirth also displayed improved HOMA-IR insulin sensitivity (p = 0.010) compared to girls born to mothers aged <30 years.

Conclusions

Increasing maternal age at childbirth is associated with a more favourable phenotype (taller stature and reduced abdominal fat) in their children, as well as improved insulin sensitivity in girls.     

Excessive Intrauterine Fluid Cause Aberrant Implantation and Pregnancy Outcome in Mice

The normal intrauterine fluid environment is essential for embryo implantation. In hydrosalpinx patients, the implantation and pregnancy rates are markedly decreased after IVF–embryo transfer, while salpingectomy could significantly improve the pregnancy rates. The leakage of hydrosalpinx fluid into the endometrial cavity was supposed to be the major cause for impaired fertility. However, the underlying mechanisms of hydrosalpinx fluids on implantation and ongoing pregnancy were not fully understood and remain controversial regarding its toxicity. In present study, by infusing different volume of non-toxic fluid (0.9% saline) into uterine lumen before embryo implantation in mice (Day4 08:30), we found that while the embryos were not “flushed out” from the uteri, the timing of implantation was deferred and normal intrauterine distribution (embryo spacing) was disrupted. The abnormal implantation at early pregnancy further lead to embryo growth retardation, miscarriage and increased pregnancy loss, which is similar to the adverse effects observed in hydrosalpinx patients undergoing IVF-ET. We further examined uterine receptivity related gene expression reported to be involved in human hydrosalpinx (Lif, Hoxa10, Integrin α(v) and β(3)). The results showed that expression of integrin α(v) and β(3) were increased in the fluid infused mouse uteri, implicating a compensatory effect to cope with the excessive fluid environment. Our data suggested that the adverse effects of excessive non-toxic luminal fluid on pregnancy are primarily due to the mechanical interference for normal timing and location of embryo apposition, which might be the major cause of decreased implantation rate in IVF-ET patients with hydrosalpinx.     

Elevated Progesterone Levels on the Day of Oocyte Maturation May Affect Top Quality Embryo IVF Cycles

In contrast to the impact of elevated progesterone on endometrial receptivity, the data on whether increased progesterone levels affects the quality of embryos is still limited. This study retrospectively enrolled 4,236 fresh in vitro fertilization (IVF) cycles and sought to determine whether increased progesterone is associated with adverse outcomes with regard to top quality embryos (TQE). The results showed that the TQE rate significantly correlated with progesterone levels on the day of human chorionic gonadotropin (hCG) trigger (P = 0.009). Multivariate linear regression analysis of factors related to the TQE rate, in conventional IVF cycles, showed that the TQE rate was negatively associated with progesterone concentration on the day of hCG (OR was -1.658, 95% CI: -2.806 to -0.510, P = 0.005). When the serum progesterone level was within the interval 2.0–2.5 ng/ml, the TQE rate was significantly lower (P <0.05) than when the progesterone level was < 1.0 ng/ml; similar results were obtained for serum progesterone levels >2.5 ng/ml. Then, we choose a progesterone level at 1.5ng/ml, 2.0 ng/ml and 2.5 ng/ml as cut-off points to verify this result. We found that the TQE rate was significantly different (P <0.05) between serum progesterone levels < 2.0 ng/ml and >2.0 ng/ml. In conclusion, the results of this study clearly demonstrated a negative effect of elevated progesterone levels on the day of hCG trigger, on TQE rate, regardless of the basal FSH, the total gonadotropin, the age of the woman, or the time of ovarian stimulation. These data demonstrate that elevated progesterone levels (>2.0 ng/ml) before oocyte maturation were consistently detrimental to the oocyte.     

Sickle Cell Disease in Pregnancy: Trend and Pregnancy Outcomes at a Tertiary Hospital in Tanzania

SCD in pregnancy is associated with increased adverse fetal and maternal outcomes. In Tanzania where the frequency of sickle cell trait is 13% there has been scanty data on SCD in pregnancy. With progressive improvement in childhood survival the burden of SCD in pregnancy will increase. We analyzed all deliveries at Muhimbili National Hospital (MNH) from 1999 to 2011. Fetal and maternal outcomes of SCD deliveries were compared with non-SCD. Data were analyzed using IBM SPSS statistics version 19. Chi square and Fisher Exact tests were used to compare proportions and the independent t-test for continuous data. To predict risks of adverse effects, odds ratios were determined using multivariate logistic regression. A p-value<0.05 was considered significant. In total, 157,473 deliveries occurred at MNH during the study period, of which 149 were SCD (incidence of 95 SCD per 100,000 deliveries). The incidence of SCD had increased from 76 per 100,000 deliveries in the 1999–2002 period to over 100 per 100, 000 deliveries in recent years. The mean maternal age at delivery was lower in SCD (24.0±5.5 years) than in non-SCD deliveries (26.2±6.0 years), p<0.001. Compared with non-SCD (2.9±0.7 Kg), SCD deliveries had less mean birth-weight (2.6±0.6 Kg), p<0.001. SCD were more likely than non-SCD to deliver low APGAR score at 5 minutes (34.5% Vs 15.0%, OR = 3.0, 95%CI: 2.1–4.2), stillbirths (25.7% Vs 7.5%, OR = 4.0, 95%CI: 2.8–5.8). There was excessive risk of maternal deaths in SCD compared to non-SCD (11.4% Vs 0.4%, OR = 29, 95%CI: 17.3–48.1). The leading cause of deaths in SCD was infections in wholly 82% in contrast to only 32% in non-SCD. In conclusion SCD in pregnancy is an emerging problem at MNH with increased adverse fetal outcomes and excessive maternal mortality mainly due to infections.     

Age- and Sex-Based Hematological and Biochemical Parameters for Macaca fascicularis

Background

The cynomolgus monkey (Macaca fascicularis) has been increasingly used in biomedical research, making knowledge of its blood-based parameters essential to support the selection of healthy subjects and its use in preclinical research. As age and sex affect these blood-based parameters, it is important to establish baseline indices for these parameters on an age and sex basis and determine the effects of age and sex on these indices.

Methods

A total of 917 cynomolgus monkeys (374 males and 543 females) were selected and segregated by age (five groups) and sex. A total of 30 hematological and 22 biochemical parameters were measured, and the effects of age and sex were analyzed.

Results

Baseline indices for hematological and biochemical parameters were separately established by age and sex. Significant effects by age, sex, and age-sex interaction were observed in a number of blood parameters. In the 49–60 months and 61–72 months age groups, red blood cell count, hemoglobulin, and hematocrit showed significantly lower values (P<0.01) in females than males. Serum alkaline phosphatase varied with age in both sexes (P<0.01) and was significantly higher in females than males (P<0.05) in the groups aged 13–24 months and 25–36 months; however, in the three groups aged over 25–36 months, serum alkaline phosphatase was significantly lower in females than males (P<0.01). Creatinine concentration increased with age (P<0.01) in all age groups; specifically in the groups aged 49–60 months and 61–72 months, creatinine was significantly higher (P<0.01) in males than females. Total protein and globulin both increased with age (P<0.01).

Conclusion

The baseline values of hematological and biochemical parameters reported herein establish reference indices of blood-based parameters in the cynomolgus monkey by age and sex, thereby aiding researchers in selecting healthy subjects and evaluating preclinical studies using this species.     

In Vitro Maturation in Women with vs. without Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

Objective

To evaluate in vitro maturation (IVM) in sub-fertile women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF), by comparing outcomes with a control group of non-PCOS.

Study design

A search strategy was developed for PubMed and studies reporting rates of the following outcomes (live birth; clinical pregnancy; implantation; cycle cancellation; oocyte maturation; oocyte fertilization; miscarriage) between patients with PCOS, PCO and controls undergoing IVM were deemed eligible. The review was conducted in accordance to the PRISMA guidelines and included studies quality was assessed through the Newcastle-Ottawa Quality scale. ORs with their corresponding 95% CIs were calculated for the main analysis and subgroup analyses were performed for PCOS cases vs. controls and PCOS vs. PCO cases. Alternative analyses were performed for live birth and clinical pregnancy, based on cycles and on women. Subgroup analyses for FSH stimulation, hCG priming and type of procedure (IVF/ICSI) were undertaken for all meta-analyses encompassing at least four study arms. Random effects models were used to calculate pooled effect estimates.

Results

Eleven studies were identified. A total of 268 PCOS patients (328 cycles), 100 PCO patients (110 cycles) and 440 controls (480 cycles) were included in the meta-analysis. A borderline trend towards higher birth rates among PCOS patients emerged (pooled OR = 1.74, 95%CI: 0.99–3.04) mainly reflected at the subgroup analysis vs. controls. Clinical pregnancy (pooled OR = 2.37, 95%CI: 1.53–3.68) and implantation rates (pooled OR = 1.73, 95%CI: 1.06–2.81) were higher, while cancellation rates lower (pooled OR = 0.18, 95%CI: 0.06-0.47) among PCOS vs. non-PCOS subjects; maturation and miscarriage rates did not differ between groups, while a borderline trend towards lower fertilization rates among PCOS patients was observed.

Conclusion

The present meta-analysis provides preliminary evidence on the effectiveness of IVM as a treatment option when offered in sub-fertile PCOS women, as the latter present at least as high outcome rates as those in non-PCOS.     

Rapid Short-Read Sequencing and Aneuploidy Detection Using MinION Nanopore Technology

MinION is a memory stick–sized nanopore-based sequencer designed primarily for single-molecule sequencing of long DNA fragments (>6 kb). We developed a library preparation and data-analysis method to enable rapid real-time sequencing of short DNA fragments (<1 kb) that resulted in the sequencing of 500 reads in 3 min and 40,000–80,000 reads in 2–4 hr at a rate of 30 nt/sec. We then demonstrated the clinical applicability of this approach by performing successful aneuploidy detection in prenatal and miscarriage samples with sequencing in <4 hr. This method broadens the application of nanopore-based single-molecule sequencing and makes it a promising and versatile tool for rapid clinical and research applications.