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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.

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.

To evaluate factors that affect a gynecologist's decision to remove an asymptomatic uterus at the time of removal of a presumed benign adnexal mass.Retrospective chart review of hysterectomies conducted when removing presumed benign adnexal masses at a tertiary-care academic center. Primary outcome was the final pathology of the adnexal mass to determine whether the hysterectomy was medically indicated. Secondary outcomes included the rate of postoperative complications.We included 185 out of 1415 charts. Most hysterectomies were performed by gynecologic oncologists (68.8%); 113 (61%) had a frozen section and of those, 76 (67.3%) were benign. Final adnexal pathology was benign in 135 (73%) cases. Using a bivariate analysis, menopausal status (P = 0.019), parity (P = 0.047), sonographic appearance of the mass (P = 0.049), and the physician's preoperative suspicion for malignancy (P 0.001) were significantly associated with the final adnexal pathology. At the multivariate level, only the physician's suspicion for malignancy was significantly associated with the final adnexal pathology (P 0.0001) with an odds ratio of 7.28 (95% confidence interval 3.11-17.02).Despite gynecologists' capacity to predict the malignant nature of an adnexal mass, 135 of 185 (73%) hysterectomies were performed without a clear medical indication, at the time of removal of benign adnexal masses.

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.

Background The last study conducted in Lebanon about postpartum depression dates back to 2014, whereas no studies have been conducted to assess postpartum anxiety (PPA). The shortage of research in this field and the potential opportunities to provide different aspects of postpartum care that respond to women's needs require a deeper understanding of the various problems faced by postpartum women. The study objectives were to delineate some factors associated with postnatal depression and anxiety among a sample of Lebanese women 4-6 weeks after delivery and validate the Edinburgh Postnatal Depression Scale (EPDS) and Perinatal Anxiety Screening Scale (PASS) in Arabic language in that sample.Methods This cross-sectional study, carried out between July 2018 and March 2019, enrolled 295 participants who came for a postnatal checkup to four clinics.Results Higher postpartum anxiety (Beta=0.25), higher insomnia (Beta=0.11) and having complications during delivery (Beta=1.81) were associated with higher postpartum depression. Higher postpartum depression score (Beta=1.38) and a premature baby birth compared to those born at term with normal weight (Beta=4.25) were associated with higher postpartum anxiety. The factor analysis for the EPDS and the PASS scales was run over the whole sample. The EPDS and PASS scales items converged over a solution of three and seven factors that had an Eigenvalue over 1 respectively, explaining a total of 64.73% and 65.12% of the variance respectively. High Cronbach’s alpha values were found for the EPDS (0.826) and PASS (0.920) scales.Conclusion Depression and anxiety prevalence rates in the Lebanese population is higher compared to other countries which may in part be due to differences of regional, social, and environmental culture. Different etiological factors could contribute to both depression and anxiety in the postpartum period, which could adversely affect both the mother and the infant.

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.

Context The role of growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) on aromatase regulation is poorly understood in humans. Objective Determine GDF9 and BMP15 effects on FSH stimulation of estradiol production in primary human cumulus granulosa cells (GCs). We hypothesized that the combination of GDF9 and BMP15 potentiates FSH-induced aromatase expression. Design Primary human cumulus GCs in culture. Setting University infertility center. Patients or Other Participants GCs of 60 women undergoing in vitro fertilization were collected. Interventions Cells were treated with GDF9 and/or BMP15 (GB) in the presence or absence of FSH, dibutyryl cAMP, or SMAD inhibitors. Main Outcome Measures Promoter activity, mRNA, protein, and estradiol levels were quantified. Results FSH and GB treatment increased CYP19A1 promoter activity, mRNA, and protein levels as well as estradiol when compared with cells treated with FSH only. GB treatment potentiated cAMP stimulation of aromatase and IGF2 stimulation by FSH. GB effects were inhibited by SMAD3 inhibitors and IGF1 receptor inhibitors. GB, but not FSH, stimulates SMAD3 phosphorylation. Conclusion The combination of GDF9 and BMP15 potently stimulates the effect of FSH and cAMP on CYP19a1 promoter activity and mRNA/protein levels. These effects translate into an increase in estradiol production. This potentiation seems to occur through activation of the SMAD2/3 and SMAD3 signaling pathway and involves, at least in part, the effect of the IGF system.

“Mystery, Medicine, and the Magnificent Mile,” the theme for the annual Midwest Reproductive Symposium International (MRSi) in Chicago, IL, captured the attention of reproductive professionals all over the world. Each year, the conference agenda encompasses emerging technologies in assisted reproduction, updates in the management of reproductive diseases, and common challenges encountered in clinical practice. The structure of the meeting, offering a mixture of lectures, panel discussions, and interactive workshops, creates a collaborative environment for physicians, geneticists, embryologists, nurses, mental health professionals, basic scientists, business administrative professionals, reproductive endocrinology and infertility fellows, and obstetrics and gynecology residents. The goal of the MRSi meeting is to provide all reproductive professionals the opportunity to exchange ideas, foster relationships, and deliver quality patient care. As the field continues to evolve, MRSi provides an exciting venue to uncover the mysteries of reproductive medicine with enthusiasm and collaboration.

Context Human granulosa cells (hGCs) produce and respond to insulin-like growth factor 2 (IGF2) but whether the oocyte participates in IGF2 regulation in humans is unknown. Objective To determine the role of oocyte-secreted factors (OSFs) such as growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) in IGF2 production by hGCs. Design Primary human cumulus GCs in culture. Setting University infertility center. Patients or Other Participants GCs of women undergoing in vitro fertilization. Intervention(s) Cells treated with GDF9 and BMP15 in the presence of vehicle, follicle-stimulating hormone (FSH), dibutyryl cyclic-AMP (dbcAMP), or mothers against decapentaplegic homolog (SMAD) inhibitors. Main Outcome Measure(s) Quantification of mRNA, protein, promoter activity, and DNA methylation. Results FSH stimulation of IGF2 (protein and mRNA) was significantly potentiated by the GDF9 and BMP15 (G+B) combination (P < 0.0001) in a concentration-dependent manner showing a maximal effect at 5 ng/mL each. However, GDF9 or BMP15 alone or in combination (G+B) have no effect on IGF2 in the absence of FSH. FSH stimulated IGF2 promoter 3 activity, but G+B had no effect on promoter activity. G+B potentiated IGF2 stimulation by cAMP. SMAD3 inhibitors inhibited G+B enhancement of IGF2 stimulation by FSH (P < 0.05) but had no effect on FSH induction. Moreover, inhibition of insulin-like growth factor receptor partially blocked G+B potentiation of FSH actions (P < 0.009). Conclusions For the first time, we show that the oocyte actively participates in the regulation of IGF2 expression in hGCs, an effect that is mediated by the specific combination of G+B via SMAD2/3, which in turn target mechanisms downstream of the FSH receptor.

Ovulation is the pinnacle of folliculogenesis, a process requiring granulosa cell (GC) proliferation and differentiation to form preovulatory follicles. In human and rodent GCs, we discovered that pituitary follicle-stimulating hormone (FSH) and insulin-like growth factors (IGFs) have interdependent effects on GC differentiation, converging on the activation of the serine/threonine kinase AKT. However, the AKT-controlled mechanisms involved in GC differentiation remain unclear. Here, we examined the role of salt-inducible kinases (SIKs), a known target of AKT, on the stimulation of GC differentiation by FSH. We first examined the expression of the three SIK isoforms in ovarian human and rat GCs and observed that SIK1 is expressed at low levels. In contrast, SIK2 and SIK3 are highly expressed with SIK3 being the strongest. Immunofluorescence of rat GCs and immunohistochemistry of rat ovaries reveal that all SIK isoforms are expressed in the GCs at levels that correlated with the mRNA levels for each isoform (SIK3>SIK2>SIK1). To determine if SIKs play any role in the response of GCs to FSH, we treated rat and human GCs with four different and specific inhibitors of SIK activity. We observed that SIK inhibition potentiated the stimulatory effect of FSH on aromatase mRNA expression, a marker of GC differentiation. This effect was also observed on aromatase protein expression and on the production of estradiol (E2). Thus, E2 levels in cells treated with FSH and SIK inhibitors were significantly higher than treatment with FSH alone. Next, to investigate whether SIK inhibition affects the transcription of the aromatase gene, we transfected rat and human primary GCs with an empty luciferase reporter or a reporter carrying the aromatase promoter. We observed that aromatase promoter activity was significantly higher in cells treated with FSH and SIK inhibitors than FSH alone. Since FSH requires the presence of the IGF1R to activate AKT, we measured SIK expression in GC-specific IGF1R knockout mice and observed that all SIK isoforms are expressed at significantly higher levels when compared to control mice, suggesting that the IGF1R is involved in repressing SIK expression. Moreover, in vivo administration of a SIK inhibitor was able to recover FSH responsiveness in GC-specific IGF1R knockout mice. These findings demonstrate for the first time the involvement of SIK in the regulation of GC differentiation and contribute to our understanding of the mechanisms regulated by FSH and IGFs in the control of aromatase expression.

The primary objective of this study is to investigate the effect of transvaginal ultrasonogram (TVUS)-guided cyst aspiration or gonadotropin releasing hormone antagonist (GnRH-ant) administration for the management of solitary ovarian cysts detected at the start of in vitro fertilization (IVF) cycles on the outcomes of the same cycles. This is a single-center, retrospective, cohort study of patients who had TVUS-guided cyst aspiration or GnRH-ant treatment for ovarian cysts detected at the start of IVF during a 5-year period. Four hundred and three patients met inclusion criteria: 41 (10.2%) underwent cyst aspiration and 362 (89.2%) were treated with GnRH-ant. There was no difference in the demographics or baseline IVF cycle characteristics of the two groups. Patients treated with GnRH-ant had a longer duration of ovarian stimulation (10.8 ± 3.45 days versus 9.05 ± 4.06 days, p = 0.003) and required higher gonadotropin doses (3887.7 ± 1097.8 IU versus 3293.7 ± 990.5 IU; p = 0.01) compared with the cyst aspiration group. There was no difference in the clinical pregnancy (43.9% versus 41.4%), spontaneous miscarriage (9.76% versus 8.01%) and live birth (34.1% versus 33.4%) rates between the groups. Our findings suggest that cyst aspiration is comparable to GnRH-ant administration for the management of solitary ovarian cysts detected at the start of IVF cycles.

PURPOSE: In vitro fertilization with trophectoderm embryo biopsy and pre-implantation genetic screening with comprehensive chromosomal screening (PGS-CCS) for aneuploidy is becoming increasingly more popular. Embryos are cryopreserved and implanted in a subsequent frozen thawed embryo transfer cycle (FET). No studies have investigated differences in pregnancy outcomes by timing of trophectoderm biopsy relative to stages of blastocyst development. METHODS: Retrospective study of all patients (n = 363) at a single IVF center between January 1, 2013 and December 31, 2016 undergoing single embryo transfer with PGS-CCS where embryos were cryopreserved with subsequent FET. Embryo expansion and grading was assessed both at the time of biopsy and transfer. Pregnancy rates were analyzed by embryo expansion and embryo grading. RESULTS: Implantation, clinical pregnancy, and live birth rates improved significantly with increased embryo expansion at the time of embryo biopsy (P

OBJECTIVE: To investigate if administration of an additional dose of gonadotropins concomitantly to human chorionic gonadotropin (hCG) trigger increases pregnancy rates in patients undergoing intrauterine insemination (IUI) with controlled ovarian hyperstimulation (COH). STUDY DESIGN: This is a retrospective cohort study of all gonadotropin-IUI cycles performed by a single physician in a private practice between January 2012 and September 2013. Control cycles were those in which follicle-stimulating hormone (FSH) was discontinued prior to the day of hCG trigger shot, and study cycles received continuous FSH including the day of hCG trigger shot. A total of 423 cycles from 239 patients were included; 275 (65.5%) were control cycles (137 patients), and 146 (34.7%) were study cycles (102 patients). RESULTS: Pregnancy rates were comparable in both control and study groups (15.27% vs. 15.07%, respectively, p=0.956). There was a 42% increase in multiple gestations in the study group; however, the difference was not statistically significant (p=0.155). Upon multivariate logistic regression, male factor infertility was the only variable that was associated with pregnancy outcomes. CONCLUSION: Continuous administration of FSH including the day of hCG trigger in patients undergoing COH with IUI does not seem to increase pregnancy rates. Our suggested protocol might be beneficial in patients with poor ovarian response.

Few published articles have compared initial hCG values across all different types of ART cycles, including cycles with fresh or frozen embryo transfer. No articles have compared initial hCG values in cycles utilizing preimplantation genetic screening (PGS). The purpose of this study is to compare initial hCG values after fresh embryo transfer, frozen embryo transfer, and after PGS. This was a single-center retrospective cohort study at an academically affiliated private IVF center. All fresh and frozen embryo transfers between January 2013 and December 31, 2015 were included. We compared mean initial serum hCG values 14 days after oocyte retrieval for fresh cycles and 9 days after frozen embryo transfer. We examined cycles of single embryo transfer (SET) and double embryo transfer (DET). Two hundred elven IVF (fresh embryo transfer), 128 FET (frozen embryo transfer cycles, no PGS), and 111 PGS cycles (ovarian stimulation with embryo cryopreservation, PGS, and frozen transfer in a subsequent estrogen-primed cycle) with initial positive hCG values were analyzed. In patients achieving a positive hCG after SET, initial hCG values were higher after PGS compared to FET (182.4 versus 124.0 mIU/mL, p = 0.02) and IVF (182.4 versus 87.1 mIU/mL, p

Introduction and objectives International agencies have recently assigned Lebanon to the group H of countries with "no national data on maternal mortality," and estimated a corresponding maternal mortality ratio (MMR) of 150 per 100,000 live births. The Ministry of Public Health addressed the discrepancy perceived between the reality of the maternal mortality ratio experience in Lebanon and the international report by facilitating a hospital-based reproductive age mortality study, sponsored by the World Health Organization Representative Office in Lebanon, aiming at providing an accurate estimate of a maternal mortality ratio for 2008. The survey allowed a detailed analysis of maternal causes of deaths. Methods Reproductive age deaths (15-49 years) were initially identified through hospital records. A trained MD traveled to each hospital to ascertain whether recorded deaths were in fact maternal deaths or not. ICD10 codes were provided by the medical controller for each confirmed maternal deaths. Results There were 384 RA death cases, of which 13 were confirmed maternal deaths (339%) (numerator). In 2008, there were 84823 live births in Lebanon (denominator). The MMR in Lebanon in 2008 was thus officially estimated at 23/100,000 live births, with an "uncertainty range" from 153 to 30.6. Hemorrhage was the leading cause of death, with double the frequency of all other causes (pregnancy-induced hypertension, eclampsia, infection, and embolism). Conclusion This specific enquiry responded to a punctual need to correct a clearly inadequate report, and it should be relayed by an on-going valid surveillance system. Results indicate that special attention has to be devoted to the management of peri-partum hemorrhage cases. Keywords Arab, postpartum hemorrhage, development, pregnancy management, verbal autopsy

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.

The objective of this study was to evaluate basal anti-Müllerian hormone as a marker for ovarian responsiveness to fertility treatment.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.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 of4 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 ofor=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).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.