Sara A. Mohamed

Human Mesenchymal Stem Cells Partially Reverse Infertility in Chemotherapy-Induced Ovarian Failure:

Introduction: Chemotherapy is the most commonly used modality to treat human cancers; however, in many cases it causes irreversible ovarian failure. In this work, we plan to evaluate the restorative function of human bone marrow mesenchymal stem cells (BMSCs) in a chemotherapy-induced ovarian failure mouse model. Methods: Acclimatized 4 to 6 week-old female mice (C57BL/6) were assigned randomly to a vehicle-treated control group (group 1), chemotherapy-treated group followed by vehicle alone (group 2), or chemotherapy-treated group followed by stem cell intraovarian injection (group 3). Outcomes were evaluated using immunohistochemistry (IHC), serum hormonal assays, and estrous cycle monitoring and breeding potential. Results: Post BMSCs administration, group 3 promptly showed detectable vaginal smears with estrogenic changes. Increase in total body weight, ovarian weight, and weight of estrogen-responsive organs (uterus and liver) was observed at 2 weeks and continued to end of the experiment. Hematoxylin and Eosin histological evaluation of the ovaries demonstrated a higher mean follicle count in group 3 than in group 2. Group 3 had lower follicle-stimulating hormone (FSH) levels (P = .03) and higher anti-Müllerian hormone serum (AMH) levels (P = .0005) than group 2. The IHC analysis demonstrated higher expression of AMH, FSH receptor, inhibin A, and inhibin B in growing follicles of group 3 versus group 2. Tracking studies demonstrated that human BMSCs evenly repopulated the growing follicles in treated ovaries. Importantly, breeding data showed significant increases in the pregnancies numbers, 2 pregnancies in group 1 and 12 in group 3 (P = .02). Conclusions: Intraovarian administered BMSCs are able to restore ovarian hormone production and reactivate folliculogenesis in chemotherapy-induced ovarian failure mouse model.

Vitamin D and corticotropin-releasing hormone in term and preterm birth: potential contributions to preterm labor and birth outcome

Abstract Background: Poor maternal vitamin D status and elevated circulating corticotropin-releasing hormone (CRH) are associated with preterm birth. It is not known if these risk factors are independent or interrelated. Both are associated with inflammation. Methods: We measured maternal circulating 25-hydroxyvitamin D (25-OH-D) and CRH from 97 samples collected from 15 early-preterm, 31 late-preterm, 21 early-term, and 30 term births. The potential involvement of vitamin D in the regulation of inflammation was evaluated by Q-PCR in human uterine smooth muscle (UTSM) cell line. Results: Maternal 25-OH-D was lowest in early-preterm births (22.9 ± 4.2 ng/ml versus 34.4 ± 1.4 ng/ml; p = .029). Circulating CRH was high in early-preterm births (397 ± 30 pg/ml). Late-preterm (304 ± 13 pg/ml) and early-term births (347 ± 17 pg/ml) were not different from term births (367 ± 19 pg/ml), after accounting for gestational age. Maternal circulating 25-OH-D and CRH were not associated in term births. In preterm births, 25-OH-D below 30 ng/ml was associated with higher CRH. Vitamin D treatment of UTSM significantly reduced mRNA for leptin and IL-6 receptors. Deletion of vitamin D receptor from UTSM promoted the expression of the cox2 inflammatory marker. Conclusion: Early-preterm birth showed a syndrome of high maternal CRH and low vitamin D status.

Atypical Presentations of Molar Pregnancy Diagnostic Roles of Imaging, β-Human Chorionic Gonadotropin Measurement, and p57 Immunostaining

In modern practice, the diagnosis of molar pregnancy is made at an early gestational age. The opportunity to diagnose gestational trophoblastic disease (GTD) using sonography alone occurs less frequently. The classic appearance of a “snowstorm” in the endometrial cavity and bilateral theca lutein cysts still applies to the diagnosis of second‐trimester GTD. The diagnosis of first‐trimester GTD requires increased clinical suspicion. If the sonographic appearance of the pregnancy is atypical, GTD should be included in the differential diagnosis. Additional nonimaging criteria such as serial quantitative β‐human chorionic gonadotropin levels, pathologic examination, and p57 (cyclin‐dependent kinase inhibitor 1C protein) immunostaining can accurately confirm the diagnosis of GTD.

Opinions and Practice of US-Based Obstetrician-Gynecologists regarding Vitamin D Screening and Supplementation of Pregnant Women

Vitamin D deficiency/insufficiency is prevalent among pregnant women. Recommendations for adequate levels of circulating 25-hydroxyvitamin D and appropriate vitamin D supplementation during pregnancy differ between the Institute of Medicine and the Endocrine Society. Obstetrician-gynecologists must make clinical decisions in this environment of uncertain guidance. An online questionnaire regarding physician practice patterns for screening and supplementing pregnant women was administered to 225 randomly selected practicing obstetrician-gynecologists of whom 101 (45%) completed the questionnaire. A majority indicated that vitamin D insufficiency was a problem in their patient population (68.4%) and that most of their pregnant patients would benefit from vitamin D supplementation (66.3%). Half (52.5%) would recommend vitamin D supplementation during pregnancy to some patients, but only 16.8% to all. Only one in four (25.8%) routinely screen their pregnant patients for vitamin D status. Physicians who indicated that vitamin D status was a problem in their patient population were more likely to screen routinely (32.8% versus 9.7%, P = 0.002) and believe their patients would benefit from supplementation (91.2% versus 16.1%, P = 0.001). Opinion regarding supplementation levels and indicators of adequacy were split between the two competing recommendations, suggesting that clinical practice will likely remain variable across physicians, with uncertain public health consequences.