Inhibin B,follicle stimulating hormone,luteinizing hormone,and estradiol and their relationship to the regulation of follicle development in girls during childhood and puberty

Inhibin B, produced by granulosa cells in the ovary, is a heterodimeric glycoprotein suppressing synthesis and secretion of the follicle stimulating hormone (FSH). The aim of the present study was to determine hormone profiles of inhibin B, FSH, luteinizing hormone (LH), and estradiol in girls during childhood and puberty and to evaluate whether inhibin B is a marker of follicle development. We examined the correlation between inhibin B and gonadotropins and estradiol during the first two years and across the pubertal development. Using a specific two-side enzyme-linked immunosorbent assay (ELISA), inhibin B levels were measured in the serum of 53 healthy girls divided into 8 groups according to age. In addition, serum FSH, LH, and estradiol were measured by chemiluminescent immunoassay in all serum samples. A rise in serum levels of inhibin B (55.2+/-7.3 ng/l, mean +/- S.E.M.) and FSH (1.78+/-0.26 UI/l), concomitant with a moderate increment of serum LH (0.36+/-0.09 UI/l) and estradiol (45.8+/-12.2 pmol/l) concentrations was observed during the first three months of life and declined to prepubertal concentrations thereafter. A strong positive correlation between inhibin B and FSH (r = 0.48, p<0.05), LH (r = 0.68, p<0.001) and estradiol (r = 0.59, p<0.01) was demonstrated during the first 2 years of life. A rise in serum levels of inhibin B, FSH, LH, and estradiol was found throughout puberty. Inhibin B had a strong positive correlation with FSH (stage I of puberty: r = 0.64, p<0.05; stage II of puberty: r = 0.86, p<0.01), LH (I: r = 0.61, p<0.05; II: r = 0.67, p<0.05), and estradiol (II: r = 0.62, p<0.05) in early puberty. From pubertal stage II, inhibin B lost this relationship to gonadotropins and estradiol. Serum inhibin B and FSH levels increased significantly during pubertal development, with the highest peak found in stage III of puberty (133.5+/-14.3 ng/l), and decreased thereafter. In conclusion, inhibin B is produced in a specific pattern in response to gonadotropin stimulation and plays an important role in the regulation of the hypothalamic-pituitary-gonadal axis during childhood and puberty in girls. Inhibin B is involved in regulatory functions in developing follicles and seems to be a sensitive marker of ovarian follicle development.     

Menopausal hormone therapy is associated with having high blood pressure in postmenopausal women: observational cohort study

Background

The relationship between menopausal hormone therapy (MHT) and cardiovascular risk remains controversial, with a number of studies advocating the use of MHT in reducing risk of cardiovascular diseases, while others have shown it to increase risk. The aim of this study was to determine the association between menopausal hormone therapy and high blood pressure.

Methods and Findings

A total of 43,405 postmenopausal women were included in the study. Baseline data for these women were sourced from the 45 and Up Study, Australia, a large scale study of healthy ageing. These women reported being postmenopausal, having an intact uterus, and had not been diagnosed with high blood pressure prior to menopause. Odds ratios for the association between MHT use and having high blood pressure were estimated using logistic regression, stratified by age (<56 years, 56–61 years, 62–70 years and over 71 years) and adjusted for demographic and lifestyle factors. MHT use was associated with higher odds of having high blood pressure: past menopausal hormone therapy use: <56 years (adjusted odds ratio 1.59, 99% confidence interval 1.15 to 2.20); 56–61 years (1.58, 1.31 to 1.90); 62–70 years (1.26, 1.10 to 1.44). Increased duration of hormone use was associated with higher odds of having high blood pressure, with the effect of hormone therapy use diminishing with increasing age.

Conclusions

Menopausal hormone therapy use is associated with significantly higher odds of having high blood pressure, and the odds increase with increased duration of use. High blood pressure should be conveyed as a health risk for people considering MHT use.     

Rat testicular testibumin is a protein responsive to follicle stimulating hormone and testosterone that shares immunodeterminants with albumin

During a search for hormonally responsive products in media from Sertoli cell enriched cultures, a major follicle stimulating hormone responsive and testosterone-responsive protein was identified and designated CMB-1. The results of the present study indicate that this protein is related immunologically to rat albumin and rat alpha-fetoprotein (AFP) and is concentrated in the testis of the adult rat. CMB-1 was therefore termed testibumin. Testibumin was purified from Sertoli cell enriched cultures to apparent homogeneity by sequential high-performance liquid chromatography on anion-exchange, chromatofocusing, gel permeation, and hydroxylapatite columns. The purified protein consists of two concanavalin A (Con A) reactive forms: one which does not interact with Con A and the other which binds to this lectin and is eluted with methyl alpha-mannoside. Testibumin is a monomer with an apparent molecular weight of 69,000 and a pI ranging between 4.5 and 4.85. The heterogeneity of this protein was further demonstrated by crossed-immunoelectrophoresis and two-dimensional gel electrophoresis. A monospecific antiserum and highly purified testibumin were used to develop a specific radioimmunoassay which permitted studies of the hormonal responsiveness of Sertoli cell enriched culture and of the content of testibumin in the reproductive tract fluids in vivo. Even though testibumin was found in serum of both sexes, it was highly concentrated in the testicular and epididymal compartments in adult rats. This protein was compared to rat serum albumin and rat AFP immunologically. With the use of immunoblots, antiserum developed against testibumin showed partial cross-reactivity with albumin and AFP when these latter proteins were denatured and were present in amounts several orders of magnitude greater than testibumin. The extent of this cross-reactivity was then examined by comparing the ability of native and S-carboxymethylated albumin to compete with 125I-testibumin for binding to a monospecific testibumin antiserum. It was shown that the unfolded derivative of albumin showed partial cross-reactivity with testibumin. We conclude that testibumin is immunologically related to albumin and AFP as these latter proteins are related to one another and that testibumin is possibly the homologue of albumin in the seminiferous tubular compartment.     

Urogenital schistosomiasis during pregnancy is associated with low birth weight delivery: analysis of a prospective cohort of pregnant women and their offspring in Gabon

An estimated 40 million women of childbearing age suffer from schistosomiasis. Animal models indicate a deleterious effect of maternal schistosomiasis on pregnancy outcomes. To date there is a lack of epidemiological evidence evaluating schistosomiasis-related morbidity in pregnancy. This study was designed to describe the impact of urogenital schistosomiasis on pregnancy outcomes in a highly endemic region of central Africa. Pregnant women attending antenatal clinics in Fougamou and Lambaréné, Gabon, were consecutively screened for the presence of Schistosoma haematobium eggs in diurnal urine samples. Maternal and newborn characteristics assessed at delivery were compared between infected and uninfected mothers. The impact of maternal schistosomiasis on low birth weight and preterm delivery was assessed using logistic regression analysis. Urogenital schistosomiasis was diagnosed in 103 (9%) of 1115 pregnant women. Maternal age was inversely associated with the prevalence of urogenital schistosomiasis, with a higher burden amongst nulliparous women. Low birth weight was more common amongst infants of S. haematobium-infected mothers. This association was unaffected by controlling for demographic characteristics, gestational age and Plasmodium infection status (adjusted Odds Ratio 1.93; 95% confidence interval: 1.08–3.42). Other risk factors associated with low birth weight delivery were underweight mothers (adjusted Odds Ratio 2.34; 95% confidence interval: 1.12–4.92), peripheral or placental Plasmodium falciparum infection (adjusted Odds Ratio 2.04; 95% confidence interval: 1.18–3.53) and preterm birth (adjusted Odds Ratio 3.12; 95% confidence interval: 1.97–4.96). Preterm delivery was not associated with S. haematobium infection (adjusted Odds Ratio 1.07 95% confidence interval: 0.57–1.98). In conclusion, this study indicates that pregnant women with urogenital schistosomiasis are at an increased risk for low birth weight deliveries. Further studies evaluating targeted treatment and prevention programmes for urogenital schistosomiasis in pregnant women and their impact on delivery outcomes are warranted.     

Endometrial thickness, Caucasian ethnicity, and age predict clinical pregnancy following fresh blastocyst embryo transfer: a retrospective cohort

Background  

In-vitro fertilization (IVF) with blastocyst as opposed to cleavage stage embryos has been advocated to improve success rates. Limited information exists on which to predict which patients undergoing blastocyst embryo transfer (BET) will achieve pregnancy. This study's objective was to evaluate the predictive value of patient and cycle characteristics for clinical pregnancy following fresh BET.     

Effects of breed, age of donor and dosage of follicle stimulating hormone on the superovulatory response of beef cows

Data were obtained on 1039 recoveries of embryos from beef cows of four breeds at two locations, in clinic and on farm. General linear models procedures were utilized to determine the effects of breed, location, age of donor, dosage of follicle stimulating hormone (FSH) and the interaction of age and FSH on the following dependent variables: 1) the mean number of ova (unfertilized oocytes and embryos) recovered; 2) the mean number and percentage of embryos (fertilized; live and dead) recovered; and 3) the mean number and percentage of transferable embryos recovered. The interaction of age of donor and dosage of FSH with breed and location prevented the pooling of data over breed and location. The mean number of ova recovered was affected by age of the donor (Charolais-in clinic), or the interaction between age of donor and dosage of FSH (Polled Hereford-in clinic and -on farm and Simmental -on farm). The mean number of embryos was affected by age of donor (Polled Hereford-in clinic), dosage of FSH (Simmental-in clinic) or their interaction (Angus-on farm). The mean number of transferable embryos was affected by age of donor (Polled Hereford-in clinic and -on farm, Simmental-in clinic and Angus-on farm). General linear models procedures were utilized to determine the effects of the embryo (stage of development and quality) and the recipient (synchrony with the donor) on the rate of pregnancy. Rate of pregnancy varied with embryo quality score and synchrony of the recipient and the embryo. In conclusion, the superovulatory response was found to be highly breed-specific, and most of the variability in embryos produced was attributed to the number of ova recovered. However, the number of ova, embryos and transferable embryos recovered was further influenced by age of the donor, dosage of FSH or their interaction.     

Molecular cloning and nucleotide sequence analysis of complementary deoxyribonucleic acid for the beta-subunit of rat follicle stimulating hormone

To provide a hybridization probe for analysis of the regulation of rat gonadotropin subunit mRNA levels, an effort was made to isolate a cloned cDNA for the beta-subunit of rat FSH (FSH beta). Using a cloned bovine FSH beta cDNA as a hybridization probe, a rat pituitary lambda gt10 cDNA library was screened and a single, strongly hybridizing clone identified. The 874 base pair cDNA insert from this clone contains the complete sequence of rat FSH beta including an amino-terminal precursor segment. Hybridization of this cloned cDNA to rat pituitary RNA demonstrated the presence of an approximately 2.0 kilobase RNA species containing FSH beta sequences. Cloned rat cDNA was also used to demonstrate that estrogen treatment of ovariectomized female rats results in decreases in mRNA concentrations for FSH beta and the beta-subunit of LH with somewhat smaller decreases in alpha-subunit mRNA concentrations. Little or no change was detected in the mRNA for the beta-subunit of TSH.     

Rainbow trout follicular maturational competence acquisition is associated with an increased expression of follicle stimulating hormone receptor and insulin-like growth factor 2 messenger RNAs

Post-vitellogenic female rainbow trout (Oncorhynchus mykiss) were assayed in vitro for follicular maturational competence (FMC). Ovarian follicles were stimulated with a range of concentrations of partially purified gonadotropin. The efficient concentration for 50% germinal vesicle breakdown (GVBD) was calculated and used as an indicator of FMC. Before in vitro assay, ovarian tissue was sampled in order to quantify mRNA abundance of specific genes in the ovarian follicle by real-time PCR. In addition, maturation-inducing steroid (MIS, 17, 20 beta-dihydroxy-4-pregnen-3-one) and estradiol (E2) plasma levels were measured by radioimmunoassay. The mRNA expression of several genes such as luteinizing hormone receptor (LH-r), follicular stimulating hormone receptor (FSH-r), insulin-like growth factor 1 (IGF1), insulin-like growth factor 2 (IGF2), insulin-like growth factor receptor 1a (IGF-r1a), and 20 beta-hydroxysteroid dehydrogenase (20 beta-HSD) that are putatively expressed in the preovulatory ovary, was studied in females of varying FMC using real-time PCR. FMC acquisition is characterized by an increase of MIS circulating levels and a concomitant drop of E2 levels. At the ovarian level, no significant variation of LH-r, 20 beta-HSD, IGF1, and IGF-r1a mRNA abundance was observed among females of varying FMC. In contrast, FSH-r and IGF2 mRNA levels were significantly higher in females exhibiting high FMC. In addition, correlation analyses showed that IGF2 and FSH-r, mRNA levels were positively correlated with FMC. These results indicate that FMC acquisition is associated with an increased expression of these gene products that may be useful markers of FMC.     

Obstetrical outcomes and maternal morbidities associated with COVID-19 in pregnant women in France: A national retrospective cohort study

BackgroundTo the best of our knowledge, no study has exhaustively evaluated the association between maternal morbidities and Coronavirus Disease 2019 (COVID-19) during the first wave of the pandemic in pregnant women. We investigated, in natural conceptions and assisted reproductive technique (ART) pregnancies, whether maternal morbidities were more frequent in pregnant women with COVID-19 diagnosis compared to pregnant women without COVID-19 diagnosis during the first wave of the COVID-19 pandemic.Methods and findingsWe conducted a retrospective analysis of prospectively collected data in a national cohort of all hospitalizations for births ≥22 weeks of gestation in France from January to June 2020 using the French national hospitalization database (PMSI). Pregnant women with COVID-19 were identified if they had been recorded in the database using the ICD-10 (International Classification of Disease) code for presence of a hospitalization for COVID-19. A total of 244,645 births were included, of which 874 (0.36%) in the COVID-19 group. Maternal morbidities and adverse obstetrical outcomes among those with or without COVID-19 were analyzed with a multivariable logistic regression model adjusted on patient characteristics. Among pregnant women, older age (31.1 (±5.9) years old versus 30.5 (±5.4) years old, respectively, p < 0.001), obesity (0.7% versus 0.3%, respectively, p < 0.001), multiple pregnancy (0.7% versus 0.4%, respectively, p < 0.001), and history of hypertension (0.9% versus 0.3%, respectively, p < 0.001) were more frequent with COVID-19 diagnosis. Active smoking (0.2% versus 0.4%, respectively, p < 0.001) and primiparity (0.3% versus 0.4%, respectively, p < 0.03) were less frequent with COVID-19 diagnosis. Frequency of ART conception was not different between those with and without COVID-19 diagnosis (p = 0.28).When compared to the non-COVID-19 group, women in the COVID-19 group had a higher frequency of admission to ICU (5.9% versus 0.1%, p < 0.001), mortality (0.2% versus 0.005%, p < 0.001), preeclampsia/eclampsia (4.8% versus 2.2%, p < 0.001), gestational hypertension (2.3% versus 1.3%, p < 0.03), postpartum hemorrhage (10.0% versus 5.7%, p < 0.001), preterm birth at <37 weeks of gestation (16.7% versus 7.1%, p < 0.001), <32 weeks of gestation (2.2% versus 0.8%, p < 0.001), <28 weeks of gestation (2.4% versus 0.8%, p < 0.001), induced preterm birth (5.4% versus 1.4%, p < 0.001), spontaneous preterm birth (11.3% versus 5.7%, p < 0.001), fetal distress (33.0% versus 26.0%, p < 0.001), and cesarean section (33.0% versus 20.2%, p < 0.001). Rates of pregnancy terminations ≥22 weeks of gestation, stillbirths, gestational diabetes, placenta praevia, and placenta abruption were not significantly different between the COVID-19 and non-COVID-19 groups. The number of venous thromboembolic events was too low to perform statistical analysis. A limitation of this study relies in the possibility that asymptomatic infected women were not systematically detected.ConclusionsWe observed an increased frequency of pregnant women with maternal morbidities and diagnosis of COVID-19 compared to pregnant women without COVID-19. It appears essential to be aware of this, notably in populations at known risk of developing a more severe form of infection or obstetrical morbidities and in order for obstetrical units to better inform pregnant women and provide the best care. Although causality cannot be determined from these associations, these results may be in line with recent recommendations in favor of vaccination for pregnant women.

In a national retrospective study, Sylvie Epelboin and colleagues investigate obstetrical outcomes and maternal morbidities among pregnant women with a COVID-19 diagnosis in France.     

Inhibin B,follicle stimulating hormone,luteinizing hormone and testosterone during childhood and puberty in males: changes in serum concentrations in relation to age and stage of puberty

Inhibin B is a gonadal dimeric polypeptide hormone that regulates synthesis and secretion of follicle stimulating hormone (FSH) in a negative feedback loop. The aim of the present study was to determine changes in serum inhibin B, gonadotropins and testosterone concentrations during childhood and puberty in males. We studied the relationship between circulating inhibin B, gonadotropins and testosterone in serum of healthy boys during the first two years of life and then in pubertal development. Using a recently developed two-side enzyme-linked immunosorbent assay (ELISA), inhibin B levels were measured in the serum of 78 healthy boys divided into eleven age groups from birth to the end of pubertal development. In addition, serum levels of gonadotropins and testosterone were measured. Serum inhibin B, gonadotropins and testosterone increased during the first months of postnatal life. A peak in serum inhibin B and gonadotropins concentrations was observed around 3-4 months of age. There was a significant positive correlation between serum inhibin B and gonadotropins and testosterone levels during the first 2 years of life. After this early increase, serum inhibin B, gonadotropins and testosterone levels decreased significantly and remained low until puberty followed by an increase beginning with the onset of puberty. Serum levels of inhibin B reached a peak at stage G3 of puberty. Around midpuberty, inhibin B lost its positive correlation with luteinizing hormone (LH) and testosterone from early puberty, and developed a strong negative correlation with FSH, which persisted into adulthood. We conclude that inhibin B plays a key role in the regulation of the hypothalamic-pituitary-gonadal hormonal axis during male childhood and pubertal development. Inhibin B is a direct marker of the presence and function of Sertoli cells and appears to reflect testicular function in boys.     

Effect of dexamethsone on luteinizing hormone and follicle stimulating hormone responses to LHRH and to clomiphene in the follicular phase of women with normal menstrual cycles.

In an attempt to elucidate the mechanism of suppressive action of glucocorticoids on the hypothalamo-pituitary-ovarian axis, we studied the effects of short-term high dose dexamethasone administration of the LH and FSH responses to LHRH and to clomiphene in healthy women with normal menstrual cycles. Seven women, 21--35 years of age, received 100 micrograms of LHRH i.v. on day 6 of two consecutive menstrual cycles, once with and once without pre-treatment with dexamethasone 2 mg orally every 6 hrs. on days 2 through 5 of the menstrual cycle. Seven other women (ages 21--35 years) received clomiphene citrate 100 mg on days 2 through 5 of their menstrual cycle, once with and once without simultaneous administration of dexamethasone 2 mg orally every 6 h. The administration of dexamethasone suppressed baseline serum levels of LH and FSH and blunted LH and FSH response to both LHRH and clomiphene. The results indicate that short-term administration of pharmacological doses of glucocorticoids suppress the secretion of LH and FSH by a direct effect on the anterior pituitary and possibly by an effect at the hypothalamic level with inhibition of the release of LHRH.     

In vitro fertilisation with recombinant follicle stimulating hormone requires less IU usage compared with highly purified human menopausal gonadotrophin: results from a European retrospective observational chart review

Background  

Previous studies have reported conflicting results for the comparative doses of recombinant follicle stimulating hormone (rFSH) and highly purified human menopausal gonadotrophin (hMG-HP) required per cycle of in vitro fertilisation (IVF); the aim of this study was to determine the average total usage of rFSH versus hMG-HP in a 'real-world' setting using routine clinical practice.     

Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study

Background

Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of endothelial nitric oxide synthase (eNOS) that is associated with endothelial dysfunction, and is a risk marker for cardiovascular disease, a significant problem in Type 1 diabetes. The aim of the present study was to measure circulating ADMA, and define its association with endothelial dysfunction and endothelial markers in people with Type 1 diabetes with low likelihood of macrovascular disease.

Methods

Sixty-one young people with Type 1 diabetes without macrovascular disease or nephropathy and 62 healthy volunteers underwent brachial artery flow-mediated dilatation (FMD) and assay of plasma ADMA and adhesion molecules.

Results

Age, gender, BMI, lipid profile and renal function were similar in the two groups. People with Type 1 diabetes had impaired FMD compared to healthy controls (5.0 ± 0.4 vs 8.9 ± 0.4%; p < 0.001). Plasma ADMA levels were significantly lower in the people with diabetes compared to healthy controls (0.52 ± 0.12 vs 0.66 ± 0.20 μmol/l, p < 0.001). Plasma ICAM-1, E-selectin and PAI-1 levels were significantly higher in people with diabetes compared to healthy controls (median 201 (IQR 172–226) vs 180 (156–216) μg/l, p = 0.027; 44.2 (32.6–60.9) vs. 33.1 (22.4–51.0) μg/l; p = 0.003 and 70.8 (33.3–85.5) vs 46.3 (23.9–76.8) μg/l, p = 0.035). Plasma ADMA and VCAM-1 levels were positively correlated (r = 0.37, p = 0.003) in people with diabetes. There was no correlation between the plasma ADMA and FMD.

Conclusion

ADMA levels are not associated with endothelial dysfunction in young adults with Type 1 diabetes without microalbuminuria or known macrovascular disease. This suggests that the impaired endothelial function in these individuals is not a result of eNOS inhibition by ADMA.     

Separating parental and treatment contributions to perinatal health after fresh and frozen embryo transfer in assisted reproduction: A cohort study with within-sibship analysis

BackgroundCompared to naturally conceived children, adverse perinatal outcomes are more common among children born after assisted reproductive technology with fresh embryo transfer (fresh-ET) or frozen embryo transfer (frozen-ET). However, most previous studies could not adequately control for family confounding factors such as subfertility. We compared birth size and duration of pregnancy among infants born after fresh-ET or frozen-ET versus natural conception, using a within-sibship design to account for confounding by maternal factors.Methods and findingsThis registry-based cohort study with nationwide data from Denmark (1994–2014), Norway (1988–2015), and Sweden (1988–2015) consisted of 4,510,790 live-born singletons, 4,414,703 from natural conception, 78,095 from fresh-ET, and 17,990 from frozen-ET. We identified 33,056 offspring sibling groups with the same mother, conceived by at least 2 different conception methods. Outcomes were mean birthweight, small and large for gestational age, mean gestational age, preterm (<37 weeks, versus ≥37), and very preterm birth (<32 weeks, versus ≥32). Singletons born after fresh-ET had lower mean birthweight (−51 g, 95% CI −58 to −45, p < 0.001) and increased odds of small for gestational age (odds ratio [OR] 1.20, 95% CI 1.08 to 1.34, p < 0.001), while those born after frozen-ET had higher mean birthweight (82 g, 95% CI 70 to 94, p < 0.001) and increased odds of large for gestational age (OR 1.84, 95% CI 1.56 to 2.17, p < 0.001), compared to naturally conceived siblings. Conventional population analyses gave similar results. Compared to naturally conceived siblings, mean gestational age was lower after fresh-ET (−1.0 days, 95% CI −1.2 to −0.8, p < 0.001), but not after frozen-ET (0.3 days, 95% CI 0.0 to 0.6, p = 0.028). There were increased odds of preterm birth after fresh-ET (OR 1.27, 95% CI 1.17 to 1.37, p < 0.001), and in most models after frozen-ET, versus naturally conceived siblings, with somewhat stronger associations in population analyses. For very preterm birth, population analyses showed increased odds for both fresh-ET (OR 2.03, 95% CI 1.90 to 2.12, p < 0.001) and frozen-ET (OR 1.66, 95% CI 1.42 to 1.94, p < 0.001) compared with natural conception, but results were notably attenuated within siblings (OR 1.18, 95% CI 1.0 to 1.41, p = 0.059, and OR 0.92, 95% CI 0.67 to 1.27, p = 0.6, for fresh-ET and frozen-ET, respectively). Sensitivity analyses in full siblings, in siblings born within 3-year interval, by birth order, and restricting to single embryo transfers and blastocyst transfers were consistent with the main analyses. Main limitations were high proportions of missing data on maternal body mass index and smoking.ConclusionsWe found that infants conceived by fresh-ET had lower birthweight and increased odds of small for gestational age, and those conceived by frozen-ET had higher birthweight and increased odds of large for gestational age. Conception by either fresh-ET or frozen-ET was associated with increased odds of preterm birth. That these findings were observed within siblings, as well as in conventional multivariable population analyses, reduces the likelihood that they are explained by confounding or selection bias.Trial registrationClinicalTrials.gov ISRCTN11780826.

Kjersti Westvik-Johari and co-workers report on perinatal outcomes following fresh and frozen embryo transfer.     

Adverse pregnancy outcomes are associated with Plasmodium vivax malaria in a prospective cohort of women from the Brazilian Amazon

BackgroundMalaria in Brazil represents one of the highest percentages of Latin America cases, where approximately 84% of infections are attributed to Plasmodium (P.) vivax. Despite the high incidence, many aspects of gestational malaria resulting from P. vivax infections remain poorly studied. As such, we aimed to evaluate the consequences of P. vivax infections during gestation on the health of mothers and their neonates in an endemic area of the Amazon.Methods and findingsWe have conducted an observational cohort study in Brazilian Amazon between January 2013 and April 2015. 600 pregnant women were enrolled and followed until delivery. After applying exclusion criteria, 329 mother-child pairs were included in the analysis. Clinical data regarding maternal infection, newborn’s anthropometric measures, placental histopathological characteristics, and angiogenic and inflammatory factors were evaluated. The presence of plasma IgG against the P. vivax (Pv) MSP1₁₉ protein was used as marker of exposure and possible associations with pregnancy outcomes were analyzed. Multivariate logistic regression analysis revealed that P. vivax infections during the first trimester of pregnancy are associated with adverse gestational outcomes such as premature birth (adjusted odds ratio [aOR] 8.12, 95% confidence interval [95%CI] 2.69–24.54, p < 0.0001) and reduced head circumference (aOR 3.58, 95%CI 1.29–9.97, p = 0.01). Histopathology analysis showed marked differences between placentas from P. vivax-infected and non-infected pregnant women, especially regarding placental monocytes infiltrate. Placental levels of vasomodulatory factors such as angiopoietin-2 (ANG-2) and complement proteins such as C5a were also altered at delivery. Plasma levels of anti-PvMSP1₁₉ IgG in infected pregnant women were shown to be a reliable exposure marker; yet, with no association with improved pregnancy outcomes.ConclusionsThis study indicates that P. vivax malaria during the first trimester of pregnancy represents a higher likelihood of subsequent poor pregnancy outcomes associated with marked placental histologic modification and angiogenic/inflammatory imbalance. Additionally, our findings support the idea that antibodies against PvMSP1₁₉ are not protective against poor pregnancy outcomes induced by P. vivax infections.