Use of Mesenchymal Stem Cells in Experimental Ovarian Damage.

BACKGROUND: Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamicpituitary- gonadal axis. OBJECTIVES: The current study investigated the therapeutic potentials of mesenchymal stem cells (MSCs) in a murine model of BPA-induced ovarian damage. METHODS: Fifty adult female rats were divided into: Group 1; control group, Group IIa, IIb: rats were given oral gavage of BPA (25 and 50 mg/Kg body weight respectively) on a daily basis for 15 days, and Group IIIa, IIIb; rats were intravenously treated with of MSCs (106 cells) after receiving the last dose of BPA as in group II. Plasma and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). A histological examination of ovarian tissue was also conducted. RESULTS: BPA resulted in a significant elevation in plasma levels of LH, FSH, and ovarian tissue levels of MDA and a significant decrease in estradiol and progesterone. All genetic and protein markers of apoptosis were elevated in BPA treated group with decreased oestrogen receptor expression in the ovarian tissue. Increased apoptotic cells were confirmed by TUNEL assay. A high dose of BPA was able to increase the number of atretic follicles in the ovarian tissue whereas the numbers of primordial, primary, secondary and Graafian follicles were decreased. All the laboratory and histological abnormalities were ameliorated by treatment with MSCs. CONCLUSION: The antioxidant and anti-apoptotic effects of MSCs could possibly explain the ability of this therapeutic modality to ameliorate BPA-induced-ovarian damage.

Vitamin D receptor gene polymorphism and polycystic ovary syndrome susceptibility.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women. This study was designed to investigate the associations of vitamin D receptor (VDR) gene variants with PCOS risk and the severity of the disease phenotype among Egyptian women. METHODS: In this study, 185 women with PCOS and 207 fertile women as controls were recruited. Cases were divided into phenotype groups based on their clinical and paraclinical features. Clinical and laboratory data were measured in the patient and control groups. All individuals were genotyped for nine single-nucleotide polymorphisms (SNPs) located across the VDR gene using TaqMan allelic discrimination real-time polymerase chain reaction. RESULTS: Women with PCOS were significantly (P ≤ 0.001) higher body mass index (BMI) (22.77 ± 2.5) than controls (21.68 ± 1.85 kg/m2). Women with PCOS had significantly higher anti-Mullerian hormone, prolactin, luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), free testosterone, total testosterone, and dehydroepiandrosterone sulfate levels than the control group (P ≤ 0.001). The level of FSH was significantly lower in women with PCOS than in the control group (P ≤ 0.001). Analysis of the VDR rs4516035, rs2107301, rs1544410 (BsmI), and rs731236 (TaqI) SNPs showed a significant association with PCOS phenotype A. Furthermore, rs2228570 (FokI), rs3782905, rs7975232 (ApaI), and rs739837 SNPs showed a significant association with PCOS phenotype C. Furthermore, rs11568820 SNP showed a significant association with PCOS phenotype D (P < 0.05). CONCLUSIONS: The findings of this study indicate that variations in the VDR gene were associated with an increased risk of PCOS in Egyptian women.

Does the Time of Starting Progesterone Luteal Support Affect Embryo Transfer in Long Agonist Protocol Downregulated ICSI Cycles? A Randomized Controlled Trial.

The aim of this study was to compare the effects of starting progesterone (P4) luteal support (LS) on day of egg retrieval (ER) or day of embryo transfer (ET) on the ratio of difficult ET and cycle outcome. This was a RCT ( ClinicalTrials.gov Identifier: NCT03040830) carried out at Mansoura Integrated Fertility Center (MIFC), Mansoura, Egypt, from November 2015 to January 2017. A total of 171 eligible long agonist ICSI cases were randomly allocated on day of ER into group A (86) starting LS as daily IM 100 mg P4 on day of ER and group B (85) starting P4-LS on day of ET. Difficult ET was defined as blood on ET catheter and/or sounding or dilating the cervix. Primary outcome was the overall ratio of difficult ET and ratios on day 3 and 5 ET. Secondary outcome was the ongoing pregnancy rate (OPR) and implantation rate (IR). The results are presented as % for groups A and B respectively: overall difficult ET (44.1, 24.7) (p = 0.009); day 3 difficult ET (23.2, 24.4) (p = 0.45); day 5 difficult ET (62.7, 25.6) (p = 0.001); overall OPR (38.3, 44.7) (p = 0.43); day 3 ET OPR (41.8, 33.3) (p = 0.51); day 5 ET OPR (34.8, 57.5) (p = 0.048); overall IR (20.0, 22.5) (p = 0.62); day 3 ET IR (17.8, 13.4) (p = 0.44); day 5 ET IR (22, 34.1) (p = 0.09). In conclusion, starting P4 luteal support on egg retrieval day is associated with significantly higher ratio of difficult embryo transfer and lower ongoing pregnancy rate and tendency to lower IR in day 5 ET, so starting P4-LS on day of ET is recommended.

Cervical pregnancy management: An updated stepwise approach and algorithm.

The aim of this short review was to present and categorizes most of updated successful interventions for cervical pregnancy (CP) management in a simple designed easily recognized diagram together with a proposed algorithm of these interventions beside author clinical experience. A comprehensive literature search was carried out in the following electronic databases, PubMed, Scopus, Embase, Google Scholar, Directory of Open Access Journals and Cochrane electronic databases. Keywords including cervical ectopic pregnancy, medical treatment, conservative management, successful interventions, uterine artery embolization and hysteroscopy were used to search these various databases. There are different successful CP management interventions reported in the literature varied from simple to complex regimens according to the patient situation, obstetrician experience and availability of health services. These approaches were categorized in a stepwise diagram and a proposed algorithm. Up till now, there is no consensus regarding the optimal CP management. To the best of knowledge, this review was unprecedented in organizing and categorizing the different successful CP management interventions. The proposed currently undertaken stepwise approach diagram and algorithm highlights the rapidly changing management of CP and open the door for further meta-analysis.

Vitamin D Status and Pregnancy Complications: Serum 1,25-di-hydroxyl-Vitamin D and its Ratio to 25-hydroxy-Vitamin D are Superior Biomarkers than 25-hydroxy-Vitamin D.

Vitamin D (VitD) deficiency during pregnancy has been associated with adverse neonatal outcomes and increased risk of late pregnancy complications. We planned to correlate serum VitD biomarkers; 25-hydroxyvitamin D (25-OH-VitD) and 1,25-dihydroxyvitamin D (1,25-diOH-VitD) levels; and their ratio with the frequency of feto-maternal pregnancy complications. A prospective cross-sectional case-control study was conducted at Aljouf Maternity and Children Hospital, Sakaka, Saudi Arabia, during the period of September 1, 2017 to September 30, 2019. 322 pregnant women were stratified into 2 groups: controls (110 cases) and complicated group (212 cases). The later comprised severe preeclamptic toxemia associated with intrauterine growth restriction (58 cases), gestational diabetes mellitus (GDM; 82 cases), abortion (26 cases), undisturbed ectopic pregnancy (16 cases), premature rupture of membranes (PROM; 14 cases), and, inevitable preterm labour (16 cases). After clinical assessment, peripheral blood samples were collected. Serum biomarkers were measured using specific immunoassays. The direct 1,25-diOH-VitD/25-OH-VitD ratio was calculated. Serum 25-OH-VitD indicated widely spreading VitD deficiency among participants with significantly higher levels in controls vs. GDM subgroup only. 1,25-diOH-VitD levels and the ratio were markedly reduced in the six complicated subgroups vs. controls, with non-significant differences amongst the complicated subgroups. ROC analysis showed very high sensitivity and specificity, to differentiate patients from controls, only for 1,25-diOH-VitD (AUC = 0.965; 0.947 - 0.983, p <0.001) followed by the ratio but not 25-OH-VitD. In conclusions, 25-OH-VitD did not show significant changes except for GDM. 1,25-diOH-VitD levels and the ratio showed strong associations with pregnancy complications. Serum 1,25-di-OH-VitD and its ratio to 25-OH-VitD are more reliable and physiologically relevant biomarkers for VitD status in pregnancy.

Prevalence, Correlates, and Barriers of Contraceptive Use among Women Attending Primary Health Centers in Aljouf Region, Saudi Arabia.

(1) Backgrounds and Objectives: with the rapid alteration in the socio-demographic pattern of the Saudi community, particularly the changes concerned with women's education and work force, contraceptive use must be a fundamental aspect in the life of women in reproductive age. The present study aimed to identify the prevalence and correlates of contraceptive use among women attending primary health centers in Aljouf region, Saudi Arabia, and to determine the perceived barriers of stopping or not using contraceptive methods in this population. (2) Methods: a primary health center-based cross-sectional study was conducted among 369 women of reproductive age. Data collection was done by using structured questionnaires distributed during face to face interviews with the participants. Data were analyzed using the SPSS program, version 24. (3) Results: most of the participants (n = 166; 45%) were current contraceptive users and 32.2% (n = 119) reported previous use of contraceptive methods. Pills were the most frequently used method (n = 203; 71.2%) and intrauterine devices (IUDs) came next (n = 67; 23.5%) while surgery was the least common method among the respondents (n = 3; 1.1%). Logistic regression analysis showed that the significant predictors of contraceptive use were: age > 35 years (odds ratio (OR): 4.52; confidence interval (CI): 1.56-15.42), Children number ≥ 4 (odds ratio (OR): 1.41; confidence interval (CI): 1.06-1.92) and monthly income ≥ 5000 Saudi Riyal (RS) (odds ratio (OR): 2.29; confidence interval (CI): 1.24-8.27). The most perceived barriers towards contraceptive utilization were cultural, demographic, medical, administrative, and barriers related to the method itself. The least reported barriers were psychosocial and physical. (4) Conclusions: the present study showed a high prevalence of contraceptive use among Saudi women in Aljouf region, Saudi Arabia. The study recommended sustained efforts to increase population awareness of the importance of family planning. Policymakers should discover the barriers that prevent contraceptive utilization by women.

The effects of timing of intrauterine insemination in relation to ovulation and the number of inseminations on cycle pregnancy rate in common infertility etiologies.

BACKGROUND: Controlled ovarian hyperstimulation with intrauterine insemination (COH/IUI) is an established tool in medically assisted conception for many infertility factors. However, the proper timing of IUI after hCG trigger and the frequency of IUI are still debated. We aimed to examine the association between the cycle pregnancy rate (CPR) and: (i) single IUI timed at 36 ± 2 h post-hCG (pre- or post-ovulation) (ii) the number of IUI (single or double) for pre-ovulatory cases both aims in male, anovulatory and unexplained infertility. METHODS: The study included a total 1146 first-stimulated cycles in infertile couples due to male factor, anovulation or unexplained infertility. Cycles were stimulated by clomiphine citrate (CC) or sequential CC-hMG or hMG and monitored by transvaginal ultrasound. When the leading follicle reached ≥ 18 mm mean diameter, 10000 IU hCG was given to trigger ovulation and IUI was timed for 36 ± 2 h later. Semen was processed and ovulation was checked at the time of IUI. Post-ovulatory cases received single IUI, while pre-ovulatory cases were sequentially randomized to receive either single or double IUI. The end-point of the cycle was CPR. RESULTS: Overall CPR in the whole cohort was 10.1%. When ovulation was present before IUI, CPR was 11.7% compared with 6.7% when ovulation was absent [OR (95% CI): 1.85 (1.12-3.06), P = 0.015]. When this OR was computed according to infertility etiology, it was 1.26 (0.52-2.95) (P = 0.82) for male factor infertility and 2.24 (1.23-4.08) (P = 0.007) for non-male factor infertility. Comparing the CPR for double versus single IUI in pre-ovulatory cases, the OR for all cycles was 1.9 (0.76-4.7) (P = 0.22), but according to etiology, it was 4.667 (0.9-24.13) (P = 0.06) in male factor and 1.2 (0.43-3.33) (P = 0.779) for non-male factors. CONCLUSIONS: Single IUI timed post-ovulation gives a better CPR when compared with single pre-ovulation IUI for non-male infertility, whereas for male factors, pre-ovulation, double IUI gives a better CPR when compared with single IUI.