May 2011.

Objective. This study aims to investigate the effect of combining calcium and vitamin D supplements with metformin on menstrual cycle abnormalities, gonadotropins, and IGF-1 system in vitamin D-deficient/insufficient PCOS women. Study Design. This is a randomized, placebo-controlled clinical trial. Setting. This study was performed in Damascus University of Obstetrics and Gynecology Hospital and Orient Hospital, in Damascus, Syria. Materials and Methods. Forty PCOS women with 25-OH-vitamin D < 30 ng/ml were randomly assigned to take either metformin (1500 mg/daily) plus placebo or metformin (1500 mg/daily) plus calcium (1000 mg/daily) and vitamin D3 (6000 IU/daily) orally for 8 weeks. Serum levels of gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-1 (IGFBP-1) were detected at the baseline during the early follicular phase of a spontaneous or induced menstrual cycle and after 8 weeks of intervention (except for the final gonadotropins levels which were assayed from samples obtained during the early follicular phase of a spontaneous menstrual cycle). Results. Thirty-four patients (85%) completed the study. After 8 weeks of intervention, calcium and vitamin D co-supplementation led to a significant increase in 25-OH-vitamin D levels and calcium levels in the supplementation group compared to the other group (change in 25-OH-vitamin D levels: +19.38 ± 7.78 vs +0.11 ± 4.79 ng/ml, respectively; p value=0.0001) (change in calcium levels: +0.83 ± 0.82 vs +0.01 ± 0.86 mg/dl, respectively; p value=0.014). An improvement in menstrual cycle irregularity was detected in 38.5% and 58.8% of patients in metformin-placebo group and metformin-calcium-vitamin D group, respectively; but the change was statistically significant only in the supplementation group (p value=0.002). Nevertheless, the means of changes from baseline in gonadotropins levels (serum levels of LH, FSH, and LH to FSH ratio) and the studied parameters of IGF-1 system (serum levels of IGF-1, IGFBP-1, and IGF-1 to IGFBP-I ratio) did not differ significantly between the two groups. Conclusions. Calcium and vitamin D supplements can support metformin effect on regulation of menstrual cycle irregularity in vitamin D-deficient/insufficient PCOS patients, but this effect is not associated with any significant changes in gonadotropins or IGF-1 system. These results suggest a possible role of calcium and vitamin D supplements in managing PCOS. However, further studies are needed to identify the underlying mechanisms. The Clinical Trial Registration Number is NCT03792984.

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Gonadotropin-releasing hormone (GnRH) analogues are commonly used in clinical practice to prevent premature luteinizing hormone (LH) surge during In-Vitro Fertilization/ Intra-Cytoplasmic Sperm Injection (IVF/ICSI) cycles. This review aimed to summarize the available evidence comparing the effects of conventional GnRH antagonist protocols, the most commonly used GnRH antagonist protocols, and GnRH agonist protocols on IVF/ICSI outcomes in women with polycystic ovary syndrome (PCOS). A comprehensive electronic search was carried out in Pubmed, Cochrane CENTRAL, Scopus, Web of Science, CINAHL, TRIP, ClinicalTrials.gov and ISRCTN registry from inception until 24 November 2020 without any language or date restrictions. In addition, reference lists of eligible studies and previous meta-analyses were hand-searched to identify relevant studies. Eligible randomized controlled trials were those designed to compare the effects of conventional GnRH antagonist protocols and GnRH agonist protocols on IVF/ICSI outcomes in PCOS subjects. The Cochrane ROB 2.0 tool was used to assess the risk of bias of each study, and the GRADE assessment was used to evaluate the overall quality of evidence. Data synthesis and analyses were done using Review Manager 5.3 with the assistance of Revman Web. A random-effects model was used for all meta-analysis. Dichotomous outcomes were reported as Relative Risk (RR) and continuous outcomes as Weighted Mean Difference (WMD), both with 95% CIs. The primary outcomes were Live birth rate, Ongoing pregnancy rate, and Ovarian hyperstimulation syndrome (OHSS) rate. Other IVF outcomes were considered secondary outcomes. We included ten studies with 1214 randomized PCOS women. Using GnRH antagonist protocols led to a significantly lower OHSS rate (RR = 0.58; 95% CI: [0.44 to 0.77], P = 0.0002), shorter stimulation duration (WMD = − 0.91; 95% CI: [-1.45 to − 0.37] day, P = 0.0009), lower gonadotropin consumption (WMD = − 221.36; 95% CI: [− 332.28 to − 110.45] IU, P < 0.0001), lower E2 levels on hCG day (WMD = − 259.21; 95% CI: [− 485.81 to − 32.60] pg/ml, P = 0.02), thinner endometrial thickness on hCG day (WMD = − 0.73; 95% CI: [− 1.17 to − 0.29] mm, P = 0.001), and lower number of retrieved oocytes (WMD = − 1.82; 95% CI: [− 3.48 to − 0.15] oocytes, P = 0.03). However, no significant differences in live birth rate, ongoing pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate and cycle cancellation rate were seen between the GnRH antagonist protocols and the long GnRH agonist one. Although more cycles were cancelled due to poor ovarian response in the GnRH antagonist protocol (RR = 4.63; 95% CI: [1.49 to 14.41], P = 0.008), similar rates of cancellation due to risk of OHSS were noticed in both groups. The differences in IVF/ICSI outcomes may arise from the different patterns of gonadotropins suppression that the GnRH analogues exhibit during the early follicular phase of IVF/ICSI cycles and the divergent direct impacts of these analogues on ovaries and endometrial receptivity. The main evidence limitation was Imprecision. Conventional GnRH antagonist protocols represent a safer and more cost-effective treatment choice for PCOS women undergoing IVF/ICSI cycles than the standard long GnRH agonist protocol without compromising the IVF/ICSI clinical outcomes. The study had no sources of financial support and was prospectively registered at PROSPERO (International Prospective Register of Systematic Reviews) under registration number (CRD42021242476).

The high prevalence of genetic abnormalities (28.41 %) in our study strongly suggests the need for routine genetic testing and counseling prior to assisted reproduction in such population with idiopathic infertility, as a result may help determine the prognosis, as well as the choice of ART. Moreover it allows specific pre-implantation genetic testing to minimize the risk of transmitting genetic defects to offspring.

IntroductionThyroid autoimmune (TAI) disease with a prevalence varying between 5 and 15%, represents the most common endocrine disorder in women with reproductive age. Not only is TAI disease five to 10 folds more common in women than men but also TAI diseases is often undiagnosed because it may be present without overt thyroid dysfunction for several years. Studies found an increased prevalence of TAI in women referred to fertility clinics compared with normal population. In this analysis we aimed to study the prevalence of TAI among women seeking fertility care in Damascus, Syria in order to understand its clinical and public health importance in population.MethodsThis study is a retrospective cross-sectional study on women patients seeking fertility care at Orient Hospital, Damascus city, Syria from April 2011 to March 2018. A total of 2526 women, with available biochemical data of anti-thyroid antibodies (anti-TPO) and anti-thyroglobulin antibodies (anti-TG) were included in our study. Thyroid stimulating hormone (TSH) titers data were also included in the statistical analysis.ResultsTAI was found positive in 559 patients (22.1%) of our studies population. TAI was more prevalent in patients with abnormal TSH levels.ConclusionThyroid autoimmunity prevalence in women seeking fertility care in Damascus, Syria was 22.1% which is significantly higher than normal population. Further studies are needed to assess the relation of these antibodies in thyroid, gynecological and other factors for the Syrian population.

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Background Obstetric morbidities represent a common hallmark manifestation of antiphospholipid syndrome (APS), with the recurrent loss of pregnancy as the main complication. The presence of antiphospholipid antibodies (APA) and its potential impact have not been established yet in infertile women seeking assisted reproduction technologies in Syria. This study aims to determine the prevalence of anticardiolipin antibodies (aCL) and lupus anticoagulation (LAC) and their association with age and the In vitro fertilization (IVF) outcomes in a large sample of Syrian women. Materials and methods The electronic patients’ records were screened and relevant data extraction was performed retrospectively. The study included 876 women who had IVF between January 2012 and January 2020 in a tertiary care hospital. Results The prevalence of APA among the included women was less than 1%. Only 5 patients had positive APA. No correlation was found between the APA levels and age. Additionally, the APA did not have an impact on neither the IVF outcomes nor the number of IVF cycles. Conclusion the added value of APS antibodies’ screening could be considered very modest when compared to its financial burden on patients since it has a very low prevalence in women having IVF.