Primary ovarian insufficiency (POI) is defined as the loss of ovarian function before 40 years of age. It clinically manifests as amenorrhea, infertility, and signs of estrogen insufficiency. POI is ...frequently induced by chemotherapy. Gonadotoxic chemotherapy reagents damage granulosa cells, which are essential for follicular function and development. Our recently published studies demonstrated that intraovarian transplantation of human mesenchymal stem cells (hMSCs) can restore fertility in a chemotherapy-induced POI mouse model. However, the regenerative mechanism underlying the hMSC effect in POI mice is not fully understood. Here, we report that the hMSC secretome increased the proliferation of human granulosa cells (HGrC1). We showed by FACS analysis that treatment of HGrC1 cells with hMSC-conditioned media (hMSC CM) stimulates cellular proliferation. We also demonstrated that the expression of steroidogenic enzymes involved in the production of estrogen, CYP19A1 and StAR, are significantly elevated in hMSC CM-treated HGrC1 cells. Our data suggest that hMSC CM stimulates granulosa cell proliferation and function, which may explain the therapeutic effect of hMSCs in our chemotherapy-induced POI animal model. Our findings indicate that the hMSC secretome may be a novel treatment approach for restoring granulosa cell and ovarian function in patients with POI.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Female infertility is a global medical condition that can be caused by various disorders of the reproductive system, including premature ovarian failure (POF), polycystic ovary syndrome (PCOS), ...endometriosis, Asherman syndrome, and preeclampsia. It affects the quality of life of both patients and couples. Mesenchymal stem cells (MSCs) have received increasing attention as a potential cell-based therapy, with several advantages over other cell sources, including greater abundance, fewer ethical considerations, and high capacity for self-renewal and differentiation. Clinical researchers have examined the therapeutic use of MSCs in female infertility. In this review, we discuss recent studies on the use of MSCs in various reproductive disorders that lead to infertility. We also describe the role of microRNAs (miRNAs) and exosomal miRNAs in controlling MSC gene expression and driving MSC therapeutic outcomes. The clinical application of MSCs holds great promise for the treatment of infertility or ovarian insufficiency, and to improve reproductive health for a significant number of women worldwide.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Follicle development is the most crucial step toward female fertility and is controlled mainly by follicle-stimulating hormone (FSH). In ovarian granulosa cells (GCs), FSH activates protein ...kinase A by increasing 3′,5′-cyclic adenosine 5′-monophosphate (cAMP). Since cAMP signaling is impinged in part by salt-inducible kinases (SIKs), we examined the role of SIKs on the regulation of FSH actions. Here, we report that SIKs are essential for normal ovarian function and female fertility. All SIK isoforms are expressed in human and rodent GCs at different levels (SIK3>SIK2>SIK1). Pharmacological inhibition of SIK activity potentiated the stimulatory effect of FSH on markers of GC differentiation in mouse, rat, and human GCs and estradiol production in rat GCs. In humans, SIK inhibition strongly enhanced FSH actions in GCs of patients with normal or abnormal ovarian function. The knockdown of SIK2, but not SIK1 or SIK3, synergized with FSH on the induction of markers of GC differentiation. SIK inhibition boosted gonadotropin-induced GC differentiation in vivo, while the genomic knockout of SIK2 led to a significant increase in the number of ovulated oocytes. Conversely, SIK3 knockout females were infertile, FSH insensitive, and had abnormal folliculogenesis. These findings reveal novel roles for SIKs in the regulation of GC differentiation and female fertility, and contribute to our understanding of the mechanisms regulated by FSH. Furthermore, these data suggest that specific pharmacological modulation of SIK2 activity could be of benefit to treat ovulatory defects in humans and to increase the propagation of endangered species and farm mammals.
Placenta previa-accreta: Risk factors and complications Usta, Ihab M.; Hobeika, Elie M.; Abu Musa, Antoine A. ...
American journal of obstetrics and gynecology,
09/2005, Volume:
193, Issue:
3
Journal Article, Conference Proceeding
Peer reviewed
The purpose of this study was to identify risk factors and complications of placenta previa-accreta (PA).
Patients with placenta previa (n
=
347) delivered over 20 years were reviewed, divided into ...PA (cases, n
=
22) and no accreta (controls, n
=
325), and compared.
Cases were older with a higher incidence of smoking and previous cesarean delivery (CS). Grandmultiparity, recurrent abortions, anterior/central placentae, and low socioeconomic status were similar. PA incidence increased with the number of previous CS: 1.9%, 15.6%, 23.5%, 29.4%, 33.3%, and 50.0% after 0, 1, 2, 3, 4, and 5 previous CS, respectively. Hypertensive disorders (odds ratio OR 13.9, 95%CI 2.1-91.2,
P
=
.006), smoking (OR 3.4, 95%CI 1.1-10.2,
P
=
.031) and previous CS (OR 7.9, 95%CI 1.7-37.4,
P
=
.009) were selected by the stepwise logistic regression analysis as predictors of PA. Cases had a longer hospital stay, a higher estimated blood loss, and need for transfusion. Cesarean hysterectomy and hypogastric artery ligation were only performed in PA cases. The 2 groups had a similar delivery gestational age and neonatal outcome.
Hypertensive disorders, smoking, and previous cesarean are risk factors for accreta in placenta previa patients. Placenta previa-accreta is associated with higher maternal morbidity, but similar neonatal outcome compared with patients with an isolated placenta previa.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background: We found that it was important to fill a gap in the literature and check the psychometric properties of the Edinburgh Postnatal Depression Scale (EPDS) and Perinatal Anxiety Screening ...Scale (PASS) in the Arabic language and delineate factors associated with postnatal depression (PPD) and anxiety (PPA) among Lebanese women 4−6 weeks after delivery. Methods: This cross-sectional study carried out between July 2018 and March 2019 enrolled 295 participants who came for a postnatal checkup at four clinics. Results: The EPDS and PASS scales’ items converged over two- and four-factor solutions, explaining 62.51% and 53.33% of the variance, respectively (KMO EPDS = 0.816, αCronbach EPDS = 0.826; KMO PASS = 0.878, αCronbach PASS = 0.920; Bartlett’s test of sphericity p < 0.001). Higher postpartum anxiety (Beta = 0.256), higher postpartum insomnia (Beta = 0.079), having hypotension during pregnancy (Beta = 2.760), and having a second (Beta = 1.663) or a third baby or more (Beta = 2.470) compared with the first one were significantly associated with higher postpartum depression. Higher postpartum depression (Beta = 1.33) was significantly associated with higher postpartum anxiety, whereas having a baby through a planned pregnancy (Beta = −4.365) and having a baby who ate regularly (Beta = −3.639) were significantly associated with lower postpartum anxiety. Conclusion: Depression and anxiety prevalence rates in the Lebanese population were higher compared with other countries, which may be due in part to the differences in regional, social and environmental culture.
Abstract Preeclampsia is a progressive, multi-system disorder of pregnancy associated with morbidity and mortality on both the mother and the fetus. Currently, research is directed at identifying ...early biomarkers of preeclampsia in order to predict its occurrence. This is important because it helps understand the pathophysiology of the disease, and thus, promises new treatment modalities. Although a clear understanding of the pathogenesis of PE remains elusive, the currently most accepted theory suggests a two-stage process. The first stage results in inadequate remodeling of the spiral arteries and leads to the second stage, whereby the clinical features of the syndrome are featured. In this review, we summarize the modalities that have been studies so far to predict preeclampsia. The use of uterine artery Doppler and several other biomarkers such as vitamin D, soluble fms-like tyrosine kinase 1/placental growth factor (sFLT1/PlGF) ratio, soluble endoglin, and a subset of T-lymphocytes has shown promising results. We are still at early stages in this advance, and no clear recommendations have been made about their clinical use to date. Further studies are still needed to improve screening strategies and evaluate the cost-effectiveness of any intervention.
The use of assisted reproductive technologies (ART) has increased steadily. There has been a corresponding increase in the number of ART-related procedures such as hysterosalpingography (HSG), saline ...infusion sonography (SIS), hysteroscopy, laparoscopy, oocyte retrieval, and embryo transfer (ET). While performing these procedures, the abdomen, upper vagina, and endocervix are breached, leading to the possibility of seeding pelvic structures with microorganisms. Antibiotic prophylaxis is therefore important to prevent or treat any procedure-related infections. After careful review of the published literature, it is evident that routine antibiotic prophylaxis is generally not recommended for the majority of ART-related procedures. For transcervical procedures such as HSG, SIS, hysteroscopy, ET, and chromotubation, patients at risk for pelvic infections should be screened and treated prior to the procedure. Patients with a history of pelvic inflammatory disease (PID) or dilated fallopian tubes are at high risk for postprocedural infections and should be given antibiotic prophylaxis during procedures such as HSG, SIS, or chromotubation. Antibiotic prophylaxis is recommended prior to oocyte retrieval in patients with a history of endometriosis, PID, ruptured appendicitis, or multiple prior pelvic surgeries.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Premature ovarian insufficiency (POI) is a highly prevalent disorder, characterized by the development of menopause before the age of 40. Most cases are idiopathic; however, in some women the cause ...of this condition (e.g.; anticancer treatment, genetic disorders, and enzymatic defects) could be identified. Although hormone-replacement therapy, the principal therapeutic approach for POI, helps alleviate the related symptoms, this does not effectively solve the issue of fertility. Assisted reproductive techniques also lack efficacy in these women. Thus, an effective approach to manage patients with POI is highly warranted. Several mechanisms associated with POI have been identified, including the lack of function of the follicle-stimulating hormone (FSH) receptor, alterations in apoptosis control, mutations in
genes, and thymulin or basonuclin-1 deficiency. The above mentioned may be good targets for gene therapy in order to correct defects leading to POI. The goal of this review is to summarize current experiences on POI studies that employed gene therapy, and to discuss possible future directions in this field.
We designed our study to evaluate the knowledge and immunization practices among Lebanese obstetricians and gynecologists (OBGYN) for women of different age groups. Anonymous questionnaires were used ...to assess the knowledge and immunization practices among OBGYN. The survey was conducted at the annual meeting of the Lebanese Society of Obstetrics and Gynecology on November 13-15, 2014. Data collected included demographics, type of practice, academic background and familiarity with vaccine guidelines. Descriptive statistical methods were used to evaluate the responses. The response rate was 54.8% (114/208). Only 62.3% (71/114) recommend vaccination(s) to pregnant women with only 25.9% of those who recommend the Tdap vaccine for pregnant women giving it during the recommended third trimester. In addition, 52.6% are unaware of the CDC/ACIP immunization schedule for women in general. However, 83.0% (93/112) of respondents are willing to integrate vaccination in their practice. Our study highlights several gaps in the knowledge of Lebanese OBGYN regarding vaccination in addition to practices that are not in full accordance with common guidelines. Measures should be taken to spread proper awareness of the proper guidelines among Lebanese practitioners.
Objective The objective of this study was to evaluate basal anti-Müllerian hormone as a marker for ovarian responsiveness to fertility treatment. Study Design Frozen basal menstrual cycle day 3 serum ...samples were evaluated retrospectively for anti-Müllerian hormone, inhibin B, and follicle-stimulating hormone levels in 123 in vitro fertilization cycles (93 patients) and compared with in vitro fertilization records. Results Anti-Müllerian hormone values correlated the best with the number of retrieved oocytes ( r = 0.539; P < .001) relative to age ( r = −0.323; P < .01), follicle-stimulating hormone ( r = −0.317; P < .01), inhibin B ( P > .05), luteinizing hormone ( P > .05), and estradiol ( r = −0.190; P < .05). Receiver operating characteristic curve analysis demonstrated that, for the prediction of <4 oocytes retrieved, anti-Müllerian hormone had the largest area under the curve (AUC = 0.81; P = .0001) relative to age ( r = 0.74; P = .005), follicle-stimulating hormone (0.71; P = .02), inhibin B (0.66; P = .03), and estradiol (0.54; P > .05). Similarly, for the prediction of ≥15 retrieved oocytes, anti-Müllerian hormone had the largest area under the curve (0.80; P = .0001) relative to age (0.63; P = .02), follicle-stimulating hormone (0.64; P = .005), inhibin B ( r = 0.57; P > .05), and estradiol (0.58; P > .05). Conclusion Anti-Müllerian hormone correlates better than age, follicle-stimulating hormone, luteinizing hormone, inhibin B, and estradiol with the number of retrieved oocytes. Receiver operating characteristic curves estimated that anti-Müllerian hormone accurately predicts ovarian responsiveness to controlled ovarian stimulation with high sensitivity and specificity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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