Chronic Stress in Pregnancy Is Associated with Low Birth Weight: A Meta-Analysis.

BACKGROUND AND OBJECTIVES: Chronic activation of the stress system has cumulative effects on the body, and it places individuals at risk for adverse health outcomes. Chronic stress has been assessed by health questionnaires in pregnancy. During the perinatal period, mothers experience increased physical and emotional demands. Chronic stress interferes with hormonal functions in mothers and infants. This meta-analysis studies the effect of maternal chronic stress during pregnancy, as assessed by established stress questionnaires, on the birth weight of their full-term infants. DESIGN AND METHODS: According to our criteria and after research collection, we obtained 107 studies and we conducted two types of analyses: a logistic (N = 22,342) and linear regression analysis (N = 7431). RESULTS: Our results show that chronic stress is associated with a statistically significant risk of low birth weight (OR = 1.50, CI 95% = [1.13; 1.99], p ≤ 0.02). CONCLUSIONS: Increased maternal chronic stress, as assessed by questionnaires, in pregnancy is associated with a low-birth-weight baby. The above meta-analysis indicates that maternal high chronic stress questionnaire scores could be used as a clinical tool in order to assess low-birth-weight risk.

Primary follicular lymphoma of the uterine cervix: A case report.

Primary non-Hodgkin lymphoma of the uterine cervix is a rare clinical entity. The present case report describes an incidence of primary cervical follicular lymphoma, diagnosed during management of concurrent cervical intraepithelial neoplasia. The present case report outlines not only the necessity of adhering to guidelines regarding the management of abnormal cervical cytology, but also the importance of expert pathological review and the need for personalized management.

Acute iv CRH administration significantly increases serum active ghrelin in postmenopausal PCOS women compared to postmenopausal controls.

PURPOSE: In women with Polycystic Ovarian Syndrome (PCOS), an increased risk of disordered eating has been described. There is growing interest regarding a possible interconnection between psychological states and increased appetite in women with PCOS. Acute stress is characterized by increased Corticotropin Releasing Hormone (CRH) secretion. The aim was to estimate the ghrelin concentrations during CRH test. METHODS: Twenty postmenopausal women with PCOS and twenty age- and BMI- matched postmenopausal control women were recruited at Aretaieion University Hospital. In the morning (9 am) all subjects had anthropometric measurements (weight, height, waist circumference) and a fasting sample for hormonal measurements. An intravenous (iv) CRH stimulation test conducted over 1 min. Serum active ghrelin levels were measured at 0, 15, 30, 60, 90, 120 min after iv CRH administration. RESULTS: The postmenopausal PCOS group had a higher waist circumference compared to postmenopausal controls. Active ghrelin concentrations increased significantly from 0 to 15 min, to 30 min, to 60 min, to 90 min and then decreased to 120 min. However, within the postmenopausal control group there were no significant changes in serum active ghrelin levels. Serum active ghrelin concentrations were significantly greater in the postmenopausal control group at 0, 15 and 120 min compared to the postmenopausal PCOS group. At 90 min active ghrelin concentrations were significantly greater in the postmenopausal PCOS group. Delta Area Under the Curve of active ghrelin (ΔAUCghr) was significantly greater in the postmenopausal PCOS group compared to controls. CONCLUSIONS: In postmenopausal PCOS, but not in postmenopausal controls, iv CRH administration induces increased serum active ghrelin secretion, suggesting a possible anti-stress adaptive mechanism. An increase in serum active ghrelin may induce hunger as a side-effect of this presumed adaptive mechanism.

Daughters of polycystic ovary syndrome pregnancies and androgen levels in puberty: a Meta-analysis.

Purpose: To provide an overview and critical analysis of the literature related to the circulating androgen levels of daughters of PCOS mothers during prepubertal and pubertal stage who have not yet been diagnosed with PCOS or precocious puberty. Methods: We critically considered and meta-analyzed observational studies comparing androgens concentration in daughters of PCOS mothers compared to daughters of mothers without PCOS. A literature search was conducted in MEDLINE, Scopus and other sources from 01/09/2021 until 01/12/2021. The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The primary outcome included total testosterone levels whereas the secondary outcomes included 17a-hydroxyprogesterone (17-OHP), androstenedione (Δ4Α) and Sex Hormone Binding Globulin (SHBG) levels respectively. Results: Our search yielded 1073 studies, 9 of which were included in our analysis. The results are presented differently according to pubertal stage. Pubertal daughters of PCOS mothers exhibited significantly higher total testosterone (pooled mean difference 14.95 (95%CI: 6.98 to 22.93), higher 17-OHP (pooled mean difference 0.11 (95%CI: 0.02 to 0.20) and lower SHBG levels (pooled mean difference -10.48 (95%CI: -16.46 to -4.61). Instead, prepubertal daughters of PCOS mothers presented greater SHBG levels (pooled mean difference 7.79 (95%CI: 0.03 to 15.54) compared to controls. No difference was found in Δ4Α levels in both groups. Conclusion: The onset of puberty is a critical point in the development of the disease and an early intervention may be imperative.

Presence of antiphospholipid antibodies is associated with increased implantation failure following in vitro fertilization technique and embryo transfer: A systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis was conducted comparing the presence of anti-phospholipid (anti-PL) antibodies between women of reproductive age, without diagnosis of antiphospholipid syndrome, who experienced at least two implantation failures following in vitro fertilization and embryo transfer (IVF-ET), and either women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET. METHODS: Systematic search of the literature and meta-analysis of the relevant studies studying presence of antiphospholipid antibodies in women experiencing at least two implantation failures in IVF-ET as compared to either women who had a successful implantation after IVF-ET or/and women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET. Six hundred ninety-four published reports were retrieved; 17 of them fulfilled the inclusion criteria set. RESULTS: Presence of either any type of anti-phospholipid or anticardiolipin antibodies or lupus-anticoagulant in women experiencing at least two implantation failures in IVF-ET was associated with increased implantation failure compared to women who had a successful implantation after IVF-ET (relative risk, RR: 3.06, 5.06 and 5.81, respectively). Presence of either anticardiolipin or lupus-anticoagulant or anti-beta2 glycoprotein-I or anti-phosphatidylserine antibodies in women experiencing at least two implantation failures in IVF-EΤ was associated with increased implantation failure compared to unselected healthy fertile women with no history of IVF-ET (RR:13.92, 6.37, 15.04 and 164.58, respectively). CONCLUSION: The prevalence of antiphospholipid antibodies, particularly that of anti-beta2 glycoprotein-I and anti-phosphatidylserine antibodies, in women experiencing at least two implantation failures in IVF-ET without diagnosis of antiphospholipid syndrome is significantly greater than either in women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET. TRIAL REGISTRATION NUMBER: PROSPERO ID: CRD42018081458.

New Incretin Combination Treatments under Investigation in Obesity and Metabolism: A Systematic Review.

The worldwide upward trend in obesity in adults and the increased incidence of overweight children suggests that the future risk of obesity-related illnesses will be increased. The existing anti-obesity drugs act either in the central nervous system (CNS) or in the peripheral tissues, controlling the appetite and metabolism. However, weight regain is a common homeostatic response; current anti-obesity medications show limited effectiveness in achieving long-term weight loss maintenance; in addition to being linked to various side effects. Combined anti-obesity medications (per os or injectable) target more than one of the molecular pathways involved in weight regulation, as well as structures in the CNS. In this systematic review, we conducted a search of PubMed and The ClinicalTrials.gov up to February 2021. We summarized the Food and Drug Administration (FDA)-approved medications, and we focused on the combined pharmacological treatments, related to the incretin hormones, currently in a clinical trial phase. We also assessed the mechanism of action and therapeutic utility of these novel hybrid peptides and potential interactions with other regulatory hormones that may have beneficial effects on obesity. As we improve our understanding of the pathophysiology of obesity, we hope to identify more novel treatment strategies.

Poor Adherence to the Screening-Based Strategy of Group B Streptococcus Despite Colonization of Pregnant Women in Greece.

Group B streptococcus (GBS) is a leading cause of serious neonatal infections. Maternal GBS colonization is associated with early- and late-onset neonatal disease (EOD/LOD). In Greece, a screening-based strategy is recommended, in which concurrent vaginal-rectal cultures should be obtained between 36 0/7 and 37 6/7 weeks' gestation. We sought to examine the level of adherence to the GBS screening guidelines and estimate the prevalence of GBS colonization among pregnant women. Although in Greece the screening-based strategy is followed, we also examined known EOD risk factors and linked them to GBS colonization. A cross-sectional study of 604 women postpartum in three hospitals and maternity clinics was conducted. Following written informed consent, data were collected via a short self-completed questionnaire and review of patients' records. In 34.6% of the enrolled pregnant women, no culture had been taken. Of the remaining, 12.8% had proper vaginal-rectal sample collections. The overall maternal colonization rate was 9.6%. At least one risk factor for EOD was identified in 12.6% of participants. The presence of risk factors was associated with positive cultures (p = 0.014). The rate of culture collection did not differ between women with or without an EOD risk factor. Adherence to a universal screening of pregnant women with vaginal-rectal cultures was poor. Despite probable underestimation of GBS carrier status, almost 1 in 10 participants were GBS positive during pregnancy. Screening of women with risk factors for EOD should, at least, be prioritized to achieve prevention and prompt intervention of EOD.

Relationship Between Maternal Bone Biomarkers and Fetal Adiposity Through Normal Pregnancy.

PURPOSE: To examine the association of maternal bone markers [sclerostin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteocalcin, 25-hydroxyvitamin D3] with fetal intra-abdominal and subcutaneous adipose tissue deposition and birthweight during normal pregnancy. METHODS: One hundred pregnant women (aged 30.4 ±â€…5.6 years, mean ±â€…SD) with prepregnancy body mass index = 24.1 ±â€…4.6 kg/m2 were seen prospectively during each trimester. At each visit they were submitted to anthropometric measurements, a fasting blood sampling, a 75-g oral glucose tolerance test, and a fetal ultrasonogram. At birth, neonates had birth weight measurement. RESULTS: In the second trimester, maternal sclerostin concentrations correlated positively with fetal abdominal circumference and birth weight; maternal sRANKL concentrations correlated positively with fetal abdominal subcutaneous fat thickness, sagittal abdominal diameter, and abdominal circumference. Fetuses born to mothers with greater (>254 ng/mL), compared to fetuses born to mothers with lower (≤254ng/mL), sRANKL concentrations had greater abdominal circumference, sagittal diameter, and abdominal subcutaneous fat thickness. Maternal serum sclerostin concentrations were the best positive predictors of birth weight. In the third trimester maternal sclerostin concentrations correlated positively with fetal sagittal abdominal diameter; maternal sRANKL concentrations positively correlated with fetal abdominal circumference and fetal abdominal sagittal diameter. CONCLUSIONS: Maternal bone markers sclerostin and sRANKL may relate to fetal intra-abdominal adipose tissue deposition through as yet unknown direct or indirect mechanisms, thus contributing to birthweight.

Pregnancy Complications in a-Thalassemia (Hemoglobinopathy H): A Case Study.

Thalassemia intermedia (TI) is a clinical definition which represents a wide spectrum of thalassemia genotypes but mainly includes patients who do not require or only occasionally require transfusion. An uncommon case of a 32-year-old Greek woman, para 1, at the 22nd week + day 3 of gestation with thalassemia intermedia (she was splenectomized), where her pregnancy was complicated with portal vein thrombosis, splenic thrombosis, and partial HELLP, is described. This is a generally uncommon event in thalassemia intermedia. She had no transfusion as her hematologist consulted and she took anticoagulation therapy. Thus, we present for the first time in the literature a case of HbH a-thalassemia pregnant woman whose pregnancy was complicated with portal vein thrombosis, splenic vein thrombosis, and partial HELLP; she was treated with anticoagulation therapy and she had a successful outcome.

Low versus high volume of culture medium during embryo transfer: a randomized clinical trial.

PURPOSE: The aim of this prospective randomized control trial was to evaluate if the use of two different volumes (20-25 vs 40-45 µl) of media used for embryo transfer affects the clinical outcomes in fresh in vitro fertilization (IVF) cycles. METHODS: In total, 236 patients were randomized in two groups, i.e., "low volume" group (n = 118) transferring the embryos with 20-25 µl of medium and "high volume" group (n = 118) transferring the embryos with 40-45 µl of medium. The clinical pregnancy, implantation, and ongoing pregnancy rates were compared between the two groups. RESULTS: No statistically significant differences were observed in clinical pregnancy (46.8 vs 54.3%, p = 0.27), implantation (23.7 vs 27.8%, p = 0.30), and ongoing pregnancy (33.3 vs 40.0%, p = 0.31) rates between low and high volume group, respectively. CONCLUSION: Higher volume of culture medium to load the embryo into the catheter during embryo transfer does not influence the clinical outcome in fresh IVF cycles. TRIAL REGISTRATION NUMBER: NCT03350646.

Myomas and Adenomyosis: Impact on Reproductive Outcome.

Among uterine structural abnormalities, myomas and adenomyosis represent two distinct, though frequently coexistent entities, with a remarkable prevalence in women of reproductive age. Various mechanisms have been proposed to explain the impact of each of them on reproductive outcome. In respect to myomas, current evidence implies that submucosal ones have an adverse effect on conception and early pregnancy. A similar effect yet is not quite clear and has been suggested for intramural myomas. Still, it seems reasonable that intramural myomas greater than 4 cm in diameter may negatively impair reproductive outcome. On the contrary, subserosal myomas do not seem to have a significant impact, if any, on reproduction. The presence of submucosal and/or large intramural myomas has also been linked to adverse pregnancy outcomes. In particular increased risk for miscarriage, fetal malpresentation, placenta previa, preterm birth, placenta abruption, postpartum hemorrhage, and cesarean section has been reported. With regard to adenomyosis, besides the tentative coexistence of adenomyosis and infertility, to date a causal relationship among these conditions has not been fully confirmed. Preterm birth and preterm premature rupture of membranes, uterine rupture, postpartum hemorrhage due to uterine atony, and ectopic pregnancy have all been reported in association with adenomyosis. Further research on the impact of adenomyosis on reproductive outcome is welcome.

Novel embryo selection techniques to increase embryo implantation in IVF attempts.

PURPOSE: The final success of an IVF attempt depends on several steps and decisions taken during the ovarian stimulation, the oocyte retrieval, the embryo culture and the embryo transfer. The final selection of the embryos most likely to implant is the final step in this process and the responsibility of the lab. Apart from strict morphologic criteria that historically have been used in embryo selection, additional information on genetic, metabolomic and morphokinetic characteristics of the embryo is recently combined to morphology to select the embryo most likely to produce a pregnancy. In this manuscript, we review the most recent information on the current methods used for embryo selection presenting the predictive capability of each one. METHODS: A literature search was performed on Pubmed, Medline and Cochrane Database of Systematic Reviews for published studies using appropriate key words and phrases with no limits placed on time. RESULTS: It seems that the combination of morphologic criteria in conjunction to embryo kinetics as documented by time-lapse technology provides the most reliable information on embryo quality. Blastocyst biopsy with subsequent comprehensive chromosome analysis allows the selection of the euploid embryos with the higher implantation potential. CONCLUSION: Embryo time-lapse imaging and blastocyst biopsy combined to comprehensive chromosome analysis are the most promising technologies to increase pregnancy rates and reduce the possibility of multiple pregnancies. However, further studies will demonstrate the capability of routinely using these technologies to significantly improve IVF outcomes.

Continuous versus cyclic oral contraceptives for the treatment of endometriosis: a systematic review.

PURPOSE: Recurrence of endometriosis after conservative surgery has been observed in 40-50 % of patients within the first 5 years. A variety of regimens such as combined oral contraceptives, GnRH agonists, danazol, and progestins have been used postoperatively to reduce recurrence rates. Oral contraceptives (oCP) have been used either in a cyclic or in a continuous (no pill-free interval) fashion. The purpose of this article was to summarize the existing evidence on the efficacy and patient compliance for the use of oCP in a continuous versus cyclic fashion following conservative surgery for endometriosis. METHODS: A systematic search of Medline identified four eligible studies. Studies were considered eligible, if they have evaluated oCP therapy, either in a cyclic or continuous regimen, after conservative surgery for endometriosis. Specifically, studies (1) reporting on women with endometriosis who were treated postoperatively with both continuous oCP and cyclic oCP, (2) written in English, (3) with minimum 6 months duration of medical treatment, and (4) with minimum 12 months duration of follow-up were considered eligible for our systematic review. Outcome measures of these eligible studies were tabulated and then analyzed cumulatively. A purely descriptive approach was adopted concerning all variables. RESULTS: Postoperative use of continuous oCP was associated with a reduction in the recurrence rate of dysmenorrhea, delay in the presentation of dysmenorrhea, reduction in nonspecific pelvic pain, and reduction in the recurrence rate for endometrioma. CONCLUSIONS: Use of oCP in a continuous fashion following conservative surgery for endometriosis is more beneficial to cyclic use.

Molecular alterations of PI3K/Akt/mTOR pathway: a therapeutic target in endometrial cancer.

It is well established that the PI3K/Akt/mTOR pathway plays a central role in cell growth and proliferation. It has also been suggested that its deregulation is associated with cancer. Genetic alterations, involving components of this pathway, are often encountered in endometrial cancers. Understanding and identifying the rate-limiting steps of this pathway would be crucial for the development of novel therapies against endometrial cancer. This paper reviews alterations in the PI3K/Akt pathway, which could possibly contribute to the development of endometrial cancer. In addition, potential therapeutic targets of this pathway with emphasis on the mTOR inhibitors are also presented.

Effect of luteal-phase support on endometrial microRNA expression following controlled ovarian stimulation.

BACKGROUND: Studies suggested that microRNAs influence cellular activities in the uterus including cell differentiation and embryo implantation. In assisted reproduction cycles, luteal phase support, given to improve endometrial characteristics and to facilitate the implantation process, has been a standard practice. The effect of different types of luteal phase support using steroid hormones in relation to endometrial miRNA profiles during the peri-implantation period has not seen described. This study was designed to evaluate the expression of miRNAs during the luteal phase following controlled ovarian stimulation for IVF and the influence of different luteal phase support protocols on miRNA profiles. METHODS: The study was approved by the Johns Hopkins Hospital Institutional Review Board. Endometrial biopsies were obtained on the day of oocyte retrieval from 9 oocyte donors (group I). An additional endometrial biopsy was obtained 3-5 days later (Group II) after the donors were randomized into three groups. Group IIa had no luteal-phase support, group IIb had luteal support with micronized progesterone (P), and Group IIc had luteal support with progesterone plus 17-beta-estradiol (P + E). Total RNA was isolated and microarray analysis was performed using an Illumina miRNA expression panel. RESULTS: A total of 526 miRNAs were identified. Out of those, 216 miRNAs were differentially regulated (p < 0.05) between the comparison groups. As compared to the day of retrieval, 19, 11 and 6 miRNAs were differentially regulated more than 2 fold in the groups of no support, in the P support only, and in the P + E support respectively, 3-5 days after retrieval. During the peri-implantation period (3-5 days after retrieval) the expression of 33 and 6 miRNAs increased, while the expression of 3 and 0 miRNAs decreased, in the P alone and in the P + E group respectively as compared to the no steroid supplementation group. CONCLUSION: Luteal support following COS has a profound influence on miRNA profiles. Up or down regulation of miRNAs after P or P + E support suggest a role(s) of luteal support in the peri-implantation uterus in IVF cycles through the regulation of associated target genes.

Cytochrome P450 1A1 (CYP1A1) gene polymorphisms and ovarian cancer risk: a meta-analysis.

This meta-analysis aims to examine whether the genotype status of MspI, Ile462Val, and Thr461Asn polymorphisms in Cytochrome P450 1A1 (CYP1A1) is associated with ovarian cancer risk. Eligible case-control studies were identified through search in MEDLINE (end of search: October 2010). Pooled odds ratios (ORs) were appropriately derived from fixed effects or random effects models. Concerning MspI polymorphism, seven studies were eligible (1,051 cases and 1,613 controls); 11 studies were eligible (1,680 cases and 3,345 controls) for Ile462Val and three studies were eligible (349 cases and 785 controls) for Thr461Asn. Ile462Val polymorphism seemed to confer elevated ovarian cancer risk concerning homozygous carriers (pooled OR = 2.65, 95 % CI: 1.40-5.03, p = 0.003, fixed effects), as well as at the recessive model (pooled OR = 2.10, 95 % CI: 1.13-3.92, p = 0.020, fixed effects); these findings were replicated upon Caucasian subjects. MspI polymorphism was not associated with ovarian cancer risk (for heterozygous TC vs TT carriers pooled OR = 1.10, 95 % CI: 0.91-1.34, p = 0.329, fixed effects; for homozygous CC vs. TT carriers pooled OR = 1.11, 95 % CI: 0.65-1.90, p = 0.693, fixed effects). With respect to Thr461Asn polymorphism a finding of borderline statistical significance emerged, pointing to marginally elevated ovarian cancer risk in heterozygous Thr/Asn carriers (pooled OR = 1.62, 95 % CI: 0.97-2.70, p = 0.066, fixed effects), but not in homozygous Asn/Asn carriers (pooled OR = 1.40, 95 % CI: 0.18-10.89, p = 0.749, fixed effects). Ile462Val status seems to represent a meaningful risk factor for ovarian cancer in Caucasians. Additional case-control studies of high methodological quality are needed in order to further substantiate and enrich the present findings. Special attention should be paid upon the design of future studies; Asian and African populations should represent points of focus.

Cytochrome P450 1A1 (CYP1A1) gene polymorphisms and cervical cancer risk: a meta-analysis.

This meta-analysis aims to examine whether the genotype status of MspI and Ile462Val polymorphisms in Cytochrome-P450 1A1 (CYP1A1) is associated with cervical cancer risk. Eligible case-control studies were identified through search in MEDLINE (end of search: October 2010). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random effects models. Concerning MspI polymorphism, six studies were eligible (722 cases and 770 controls); four studies were eligible (350 cases and 519 controls) for Ile462Val. MspI polymorphism was associated with elevated cervical cancer risk (for heterozygous TC vs. TT carriers OR = 1.50, 95% CI: 0.93-2.42, random effects; for homozygous CC vs. TT carriers OR = 2.66, 95% CI: 1.14-6.19, random effects). Similarly, Ile462Val polymorphism was associated with elevated cervical cancer risk (for heterozygous Ile/Val vs. Ile/Ile carriers OR = 2.36, 95% CI: 1.10-5.08, random effects; for homozygous Val/Val vs. Ile/Ile carriers OR = 2.73, 95% CI: 1.21-6.15, fixed effects). The results were replicated upon Caucasian subjects, who represented the majority of existing data. The two examined CYP1A1 genotype polymorphisms seem to confer additional risk for cervical cancer. Accumulation of further data seems mandatory for future race-specific analyses and for the demonstration of CYP1A1-smoking interactions.

The impact of luteal phase support on endometrial estrogen and progesterone receptor expression: a randomized control trial.

BACKGROUND: To assess the impact of luteal phase support on the expression of estrogen receptor (ER) alpha and progesterone receptors B (PR-B) on the endometrium of oocyte donors undergoing controlled ovarian hyperstimulation (COH). METHODS: A prospective, randomized study was conducted in women undergoing controlled ovarian hyperstimulation for oocyte donation. Participants were randomized to receive no luteal support, vaginal progesterone alone, or vaginal progesterone plus orally administered 17 Beta estradiol. Endometrial biopsies were obtained at 4 time points in the luteal phase and evaluated by tissue microarray for expression of ER alpha and PR-B. RESULTS: One-hundred and eight endometrial tissue samples were obtained from 12 patients. No differences were found in expression of ER alpha and PR-B among all the specimens with the exception of one sample value. CONCLUSIONS: The administration of progesterone during the luteal phase of COH for oocyte donor cycles, either with or without estrogen, does not significantly affect the endometrial expression of ER alpha and PR.