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Activated protein C resistance (APCR) is a common thrombophilia, caused mainly by a mutation. The impact of APCR on the efficacy of In Vitro Fertilization (IVF) are still unclear, and no solid recommendations for its management were published. To investigate the effect of APCR on IVF outcomes and assess the efficacy of our management protocol, we retrospectively scanned the medical records of women who were tested with APCR assay in 2019 at our fertility centre. The 66 women (12%) positive for APCR had lower odds of reaching clinical pregnancies after IVF 0.18 [95% CI: 0.07–0.47] and fewer live births. The administration of low-molecular-weight heparin and aspirin associated with more implantation in treated compared to untreated APCR-positive women with an odds ratio of 43.2 [7.51–248.6]. In conclusion, APCR negatively affects the number of clinical pregnancies after IVF, but anticoagulation therapy can mitigate this effect and significantly increase clinical pregnancies.Impact StatementWhat is already known on this subject? The evidence about the impact of APCR on IVF outcomes is still inconclusive. According to the Canadian guideline, routine screening for thrombophilia in patients with recurrent pregnancy loss is not recommended. No clear recommendations regarding the management of APCR in the planning for IVF are yet available.What do the results of this study add? APCR significantly increases implantation failure among infertile women who conduct IVF. Management of APCR using LMWH and aspirin was effective in mitigating this effect and increasing successful implantation.What are the implications of these findings for clinical practice and/or further research? Our findings can support the recommendation to include APCR assay in the routine tests for infertile women conducting IVF, and suggest the combination between LMWH and aspirin as an effective therapy to increase successful implantation in APCR positive candidates. However, more controlled clinical trials are still needed to confirm our results. What is already known on this subject? The evidence about the impact of APCR on IVF outcomes is still inconclusive. According to the Canadian guideline, routine screening for thrombophilia in patients with recurrent pregnancy loss is not recommended. No clear recommendations regarding the management of APCR in the planning for IVF are yet available. What do the results of this study add? APCR significantly increases implantation failure among infertile women who conduct IVF. Management of APCR using LMWH and aspirin was effective in mitigating this effect and increasing successful implantation. What are the implications of these findings for clinical practice and/or further research? Our findings can support the recommendation to include APCR assay in the routine tests for infertile women conducting IVF, and suggest the combination between LMWH and aspirin as an effective therapy to increase successful implantation in APCR positive candidates. However, more controlled clinical trials are still needed to confirm our results.

Background: to assess the effect of female smoking on in-vitro fertilization (IVF) outcome. Methods: A total of 186 women undergoing IVF treatment cycle at Orient Hospital between December 2020 and December 2021 were classified into two groups smokers and non-smokers (93 patients for each group). An analysis of this prospective cohort study was done , where the outcome involved the following: number of oocytes retrieved, number of Metaphase II oocytes (MII), oocytes quality, maturation rate, fertilization rate, embryos' quality )embryos grade I) and clinical pregnancy rate. Results: the only significant difference was found in the number of grade I embryos which was lower in smokers’ group (p-value= 0.017Conclusion: Female smoking was associated with decreased quality of embryos (lower number of grade I embryos in smokers’ group) which may affect cumulative pregnancy rate.

In Syria, medical students were placed on call to provide sufficient human resources during COVID-19 pandemic. This research aimed to explore the ability and willingness of the final-year medical students to assist during COVID-19 in the Syrian war-torn and fragile health-system. Final-year Syrian medical students were approached between 9th-17th April 2020 through an online questionnaire. Students' COVID-19-related medical knowledge (5-point score), clinical judgement (5-point score), and preparedness and willingness to integrate in healthcare facilities were assessed. A 10-point score was created, and linear regression and Tukey's HSD test were conducted. 1673 valid responses were received, of which 1199 (71.66%) responses were from the final-year students. Of the latter, 728 (60.71%) scored 4 points or higher in the medical knowledge score (mean 3.69 points), while 298 (24.85%) scored 4 or higher in the clinical judgement score. Final-year students scored significantly higher than the fourth-year students in the clinical judgement score. Finally, 682 (56.88%) of the final-year students expressed willingness to volunteer with healthcare teams. Final-year medical students may provide medical aid, on voluntary basis, by working in fragile health systems during pandemics. However, this should be undertaken in cases of extreme need. Sufficient personal protective measures, intensive training, and adequate supervision should be guaranteed.

Background Consanguineous marriage is widely practised across the world. Its effect on acute lymphoblastic leukaemia (ALL) is controversial as both parents share some of the genes which might increase the incidence of sharing recessive genes. However, other theories suggest that consanguinity might have a protective factor as it does for other types of cancers. This study aims to study childhood ALL and consanguinity. Methods This is a case-control study, conducted in the major paediatric hospital in Damascus, Syria, using medical records. Case group included children with ALL, while control group included other patients and were matched by gender and age. Results This study comprised 386 patients, 193 of which were cases. Overall, 136 were of consanguineous marriages (36.8%), and there was no difference in consanguinity overall between cases and controls. However, when only comparing non-consanguineous parents and fourth-degree consanguinity, fourth degree was significantly higher among case group, suggesting a negative correlation OR = 0.387 (0.187–0.801) in contrast to third-degree consanguinity which was no significantly different when comparing the two groups (p > 0.05). We found no significant association between ALL and having a family history of cancer (p > 0.05) or between parents’ educational level and case-control groups (p > 0.05). Conclusion Our research suggests a negative association between fourth-degree consanguinity and childhood leukaemia. This was not observed with a third-degree consanguinity. Previous studies had contradicting data on consanguinity and ALL which demonstrates the need for further research.

Vitamin D has recently raised a great deal of controversy, not because of its traditional role of absorbing calcium and maintaining bone health, but because of its unconventional role as an endocrine factor and the extent of its impact when linked to its specific receptors (VDR) found in different tissues. Research has raced trying to find its different roles in those tissues and its association with different clinical or medical conditions, and among these cases, its role in reproductive functions and fertility in women, these studies conflicted between supporting and denying the role of vitamin D in reproductive function and rejecting this hypothesis according to the results of their study.The in vitro fertilization process allowed us to study the possible hypotheses, as this technique provides an opportunity to study the relationship between vitamin D levels with the in vitro fertilization outcomes, thus providing us with an idea of the relationship of vitamin D with fertility in women. In order to study this relationship, we designed our research as a cross-sectional study to confirm or deny this claim. Vitamin D was measured in the blood and in the follicular fluid for all cases using the electrochemiluminescence immunoassay (ECLIA) for the assay of total vitamin D, then IVF outcomes were compared with the levels of vitamin D in the blood.the levels of vitamin D are not related to the criteria of eggs such as the number of eggs and the maturity rate (MR) of eggs, but they are correlated in a statistically significant manner with the fertility rate (FR), and at the same time the levels of vitamin D in the blood were completely independent of the clinical pregnancy rate (CPR).blood vitamin D levels will affect the FR when its levels in the blood drop below a specified value, vitamin D did not correlate with the CPR. In the long run, there is scope for more research projects on vitamin D. Future research could include case-control studies of patients on vitamin D supplementation, and the study of its correlation with IVF outcomes.

A 25-year-old patient was referred to the fertility clinic in our hospital, complaining of primary infertility for 3 years. The patient reported having irregular menses, and physical examination showed clinical hirsutism, while transvaginal ultrasound revealed polycystic ovarian morphology. Hormonal workup showed elevated Anti-Müllerian Hormone (7 ng/ml), and normal levels of prolactin and thyroid stimulating hormone. Hysterosalpingogram revealed bilateral obstruction of fallopian tubes. Semen analysis of the husband was within normal limits.

COVID-19 ignited a global pandemic that, in Syria, further strained a nation and its healthcare system already ravaged by years of war and sanctions. The first case in Syria was reported on March 22, 2020, and this is the first study that aimed to describe the clinical characteristics, comorbidities, and prognosis of COVID-19 patients in Syria.Demographic and clinical data for this cross-sectional prospective study were collected on COVID-19 patients with positive polymerase chain reaction tests who were admitted to Al Assad and Al Mouwasat university hospitals between April 1 and January 31 of 2021.This study included 701 patients. The majority were over age 60 (59%) and male (67.9%). The commonest symptoms were fever (86.6%) and shortness of breath (75.6%). The commonest comorbidities were hypertension (53.9%) and diabetes mellitus (41.5%). On multivariable analysis, risk factors found to be significantly associated with poor outcomes were advanced age (≥60 years); male gender; high respiratory rate (35); respiratory failure (PaO₂/FiO₂ ratio100); heart failure; chronic lung disease; elevated white blood cell counts, lactate dehydrogenase, c-reactive protein; prolonged international normalized ratio; and low lymphocyte counts. The clinical outcomes of our patients were as follows: 59.2% improved and were discharged from the hospital, 3.5% were discharged with persistent symptoms and 37.2% died.Several biomarkers can serve as early warning and prognostic indicators of severe illness and mortality from COVID-19 in the highest risk patients, especially males with multiple comorbidities over 60 years of age. In the context of a national healthcare system stretched thin by years of civil war and sanctions, and high COVID-19 mortality rates as a consequence, extra care should be taken to use the predictive power of these biomarkers to stratify high-risk patients in the earliest possible stages of the disease to minimize severe illness and reduce fatalities.

Gonadotropin-releasing hormone (GnRH) analogues are used to prevent premature luteinizing hormone (LH) surge during In-Vitro Fertilization. However, the follicular fluid levels of the Placental growth factor (FF PlGF), the novel angiogenic factor, differ significantly between GnRH-agonist and GnRH-antagonist protocols. Thus, we compared the IVF/ICSI outcomes and their correlations with FF PlGF levels in polycystic ovary syndrome (PCOS) and normo-ovulatory women during different hyperstimulation protocols.This case-control study is a re-analysis of two prospective trials that were conducted on women who were referred to Orient Hospital, Damascus, Syria, from December 2019 to August 2021. A total of 75 PCOS-women (PCOS-Agonist, n = 53; PCOS-Antagonist, n = 22) and 83 normo-ovulatory women (Control-Agonist, n = 50; Control-Antagonist, n = 33) were included. Follicular fluid samples were collected on retrieval day.Although PCOS-women were stimulated using lower gonadotropin doses, the Ovarian-sensitivity-indexes were higher in PCOS-groups (PCOS-Agonist vs Control-Agonist; P-value0.001), (PCOS-Antagonist vs Control-Antagonist; P-value = 0.042). However, FF PlGF levels, maturation rate, fertilization rate, and oocytes morphology were comparable between PCOS and controls independently of the protocol used. Interestingly, FF PlGF levels were positively correlated with Ovarian-sensitivity-indexes in the PCOS-Antagonist, Control-Agonist, and Control-Anta groups, but not in the PCOS-Agonist group. Nevertheless, FF PlGF levels were comparable between pregnant and non-pregnant women in all studied groups.Although PCOS exaggerates ovarian response to stimulation irrespective of the protocol used, it does not have a detrimental impact on oocytes morphology or competence. Moreover, FF PlGF levels could be a marker of the ovarian response other than a predictor of pregnancy achievement.

Background Anti-Müllerian hormone (AMH) is a glycoprotein that plays an important role in the regulation of ovarian folliculogenesis. However, the data link between its follicular fluid levels (FF AMH) and the IVF/ICSI outcomes in polycystic ovary syndrome (PCOS) women are limited, contradicted, and mainly obtained from Long-GnRH agonist cycles. Thus, we conducted this study to compare the correlations between the FF AMH levels and the IVF/ICSI outcomes in PCOS women during different controlled hyperstimulation protocols. Methods The current study is a re-analysis of our previous work. The data were adopted from a prospective trial that was conducted on women who were referred to the Assisted Reproductive Unit of Orient Hospital, Damascus, Syrian Arab Republic, from December 2019 to August 2021. A total of 75 PCOS women (Rotterdam criteria) (GnRH agonist group, PCOS-A, n = 53; GnRH antagonist group, PCOS-Anta, n = 22) were included. Follicular fluid samples were collected on the retrieval day, and the FF AMH levels were measured using ELISA Kits. In addition, the embryological and clinical IVF/ICSI outcomes were detected. Spearman rank correlation coefficients were computed to assess the correlations among the studied parameters. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the accuracy of FF AMH levels in predicting pregnancy rates. Results The patients’ baseline characteristics were comparable between the PCOSA and the PCOSAnta groups. FF AMH levels were negatively correlated with the total FSH dose, the number of retrieved, MII, MI, germinal vesicle, immature, and fertilized oocytes, and with the number of obtained embryos in the PCOSA group, but not in the PCOSAnta one. Nevertheless, there were not any correlations between FF AMH levels and the rates of oocyte maturation or fertilization, or with the highquality embryo rate, embryos cleavage rate or implantation rate in any of the studied groups. In addition, no significant differences were noted in FF AMH levels between pregnant and non-pregnant women in any of the studied groups, which also was confirmed by the Receiver Operating Characteristic (ROC) Curve analysis. Discussion Since the FF AMH levels do not correlate with the maturation rate, fertilization rate, or embryos cleavage rate, the negative correlations in the PCOSA group arise from the negative impacts of the FF AMH on the number of retrieved oocytes. During the long agonist protocol, since PCOS follicles have good follicular angiogenesis, the number of retrieved oocytes would mostly depend on the negative effects of the FF AMH on folliculogenesis. However, during the GnRH antagonist protocol, the limited angiogenesis acts together with the high levels of FF AMH to reduce the number of retrieved oocytes. Conclusions High FF AMH negatively affects ovarian folliculogenesis during both; the long GnRH agonist protocol and the flexible GnRH antagonist one. However, the different patterns of follicular angiogenesis during the two protocols would affect the dependency of the oocytes' yield on the follicular fluid levels of AMH. Study registration: The data were adopted from a prospective clinical trial that was registered on the clinicaltrials.gov site by registration numbers NCT04727671.

Background 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. However, based on our recent work, the follicular fluid levels of the Placental growth factor (FF PlGF), the novel angiogenic factor, differ significantly between GnRH agonist and GnRH antagonist protocols. Thus, we conducted this study to compare the IVF/ICSI outcomes and their correlations with FF PlGF levels in polycystic ovary syndrome (PCOS) women and normo-ovulatory women during different controlled hyperstimulation protocols. Methods The current study is a re-analysis of our previous work. The data were adopted from two prospective trials that were conducted on women who were referred to the Assisted Reproductive Unit of Orient Hospital, Damascus, Syrian Arab Republic, from December 2019 to August 2021. A total of 75 PCOS women (Rotterdam criteria) (GnRH agonist group, PCOSA, n = 53; GnRH antagonist group, PCOSAnta, n = 22) and 83 normo-ovulatory women (GnRH agonist group, ControlA, n = 50; GnRH antagonist group, ControlAnta, n = 33) were included. Follicular fluid samples were collected on the retrieval day, and the FF levels of Placental growth factor (PlGF) and Anti-Müllerian hormone (AMH) were measured using ELISA Kits. Before being subjected to ICSI, the mature oocytes from both groups were morphologically assessed under an inverted microscope at 400x magnification. In addition, the embryological and clinical IVF/ICSI outcomes were detected. Spearman rank correlation coefficients were computed to assess the correlation among the studied parameters. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the accuracy of follicular fluid PlGF levels in predicting pregnancy rates. Results There were not any significant differences between PCOSA and ControlA groups or PCOSAnta and ControlAnta groups at baseline characteristics. Although PCOS women were stimulated using lower doses of gonadotropins (PCOSA = 1868.40 ± 668.29 IUs vs ControlA = 2523.00 ± 1034.11 IUs; P value

Background: 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. However, the impacts of the GnRH analogues on the follicular microenvironment in women with polycystic ovary syndrome (PCOS) are still not elucidated.Settings: This study was performed at Orient Hospital, Damascus, Syrian Arab Republic, from December 2019 to August 2021.Methods: In this interventional, prospective, parallel, non-randomized, open-label controlled clinical trial, a total of 75 PCOS women (Rotterdam criteria) were allocated to take either the long GnRH agonist protocol (n=53) or the flexible GnRH antagonist protocol (n=22). The trial was originally designed to be a randomized control trial. However, due to a lack in the drug supply during a certain point of the study duration, we used a non‐random study design. Follicular fluid (FF) samples were collected on the retrieval day, and the FF levels of Placental growth factor (PlGF) and Anti-Müllerian hormone (AMH) were measured using ELISA Kits. Before being subjected to ICSI, the mature oocytes from both groups were morphologically assessed under an inverted microscope at 400x magnification. In addition, the embryological and clinical IVF/ICSI outcomes were detected.Results: The two groups did not differ significantly at baseline characteristics. The FF PlGF levels were significantly lower, while FFAMH levels were insignificantly higher in the GnRH antagonist group (FF PlGF; GnRH agonist = 142.75 ± 51.48 pg/ml vs. GnRH antagonist = 117.70 ± 35.86 pg/ml; P value = 0.028). (FF AMH; GnRH agonist = 13.62 ± 15.25 ng/ml vs. GnRH antagonist = 16.93 ± 18.08 ng/ml; P value = 0.492). The stimulation duration was significantly lower in the GnRH antagonist group compared to the long-agonist one (GnRH agonist = 8.04 ± 0.81 days vs. GnRH antagonist = 7.64 ± 1.22 days; P value = 0.011). On the other hand, although the consumed dose of gonadotropin was lower in the antagonist group, the difference between the two groups was not statistically significant (GnRH agonist = 1868.40 ± 668.29 IUs vs. GnRH antagonist = 1779.55 ± 702.87 IUs; P value = 0.432). Similarly, the number of retrieved oocytes, MII oocytes, MI oocytes, GV oocytes, fertilized oocytes, and embryos obtained were lower in the GnRH antagonist group, but the differences between the two groups were not statistically significant. In addition, there were not any significant differences between the two groups in oocytes morphology or other embryological or clinical IVF/ICSI outcomes.Conclusions: Flexible GnRH antagonist protocol and the long GnRH agonist protocol regulate the follicular microenvironment and angiogenesis differently in PCOS subjects. However, these differences have no influence on the oocyte’s morphology or the IVF/ICSI clinical outcomes. Thus, since flexible GnRH antagonist protocol represents a more friendly and cost-effective protocol, it may be a better treatment choice for PCOS women undergoing IVF/ICSI.Study registration: This trial was prospectively registered at clinicaltrials.gov site under registration number (NCT04727671).

Background Gonadotropin-releasing hormone (GnRH) analogues are commonly used to prevent premature luteinizing hormone (LH) surge during In-Vitro Fertilization/ Intra-Cytoplasmic Sperm Injection (IVF/ICSI) cycles in routine practice. However, it is still unclear whether they have different effects on the follicular microenvironment in normo-ovulatory women. Settings: This study was performed at Orient Hospital, Damascus, Syrian Arab Republic, from December 2019 to August 2021. Methods In this interventional, prospective, parallel, non-randomized, open-label controlled clinical trial, a total of 83 normo-ovulatory women were allocated to take either the long GnRH agonist protocol (n = 50) or the flexible GnRH antagonist protocol (n = 33). The trial was originally designed to be a randomized control trial. However, due to a lack in the drug supply during a certain point of the study duration, we used a non-random study design. Follicular fluid (FF) samples were collected on the retrieval day, and the FF levels of Placental growth factor (PlGF) and Anti-Müllerian hormone (AMH) were measured using ELISA Kits. Before being subjected to ICSI, the mature oocytes from both groups were morphologically assessed under an inverted microscope at 400x magnification. In addition, the embryological and clinical IVF/ICSI outcomes were detected. Results The two groups did not differ significantly in any of the baseline characteristics. The FF PlGF levels were significantly lower, while FFAMH levels were insignificantly higher in the GnRH antagonist group (FF PlGF; GnRH agonist = 140.46 ± 42.46 pg/ml vs. GnRH antagonist = 120.49 ± 35.07 pg/ml; P value = 0.029). (FF AMH; GnRH agonist = 7.40 ± 5.69 ng/ml vs. GnRH antagonist = 8.51 ± 7.93 ng/ml; P value = 0.440). The stimulation duration was significantly shorter in the GnRH antagonist group compared to the long-agonist one (GnRH agonist = 8.28 ± 1.09 days vs. GnRH antagonist = 7.26 ± 0.89 days; P value

Objective: This study aimed to assess the protective measures among health-care workers (HCWs) in a war-torn area during coronavirus disease 2019 (COVID-19) pandemic. Methods: An online cross-sectional questionnaire was administrated to HCWs in Syria between April 1 and May 21, 2020. The questions aimed to assess the HCWs’ application of safety, hygiene, and necessary protection considerations while attending to suspected or proven COVID-19 cases. Unpaired t-test and 1-way analysis of variance (ANOVA) were used for statistical analysis. Results: Of the 290 participants included in the statistical analysis, 250 were medical doctors. Low scores of protective practices were noticed among the participants, as only 12% of doctors had a score above 6/15 points, and only 37.5% of nurses had a score of more than 4/12 points. Medical doctors who were not on the frontlines scored significantly higher than those who were on the frontlines (4.69 vs 3.80 points, respectively; P < 0.001). Conclusions: More courses and training sessions should be implemented to improve the practice of protective measures among HCWs (frontliners in particular) in areas with fragile health systems, such as Syria, during the COVID-19 pandemic, especially those on the frontlines. Moreover, specific COVID-19 protection measures guidelines to low-income countries are needed.

BackgroundGonadotropin-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). MethodsA 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. 2 Resultswe included ten studies with 1214 randomized PCOS women. Using GnRH antagonist protocols led to a significantly 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), lower number of retrieved oocytes (WMD=-1.82; 95% CI: [-3.48 to-0.15] oocytes, P=0.03), and lower OHSS rate (RR= 0.58; 95% CI: [0.44 to 0.77], P=0.0002). However, no significant differences in live birth rate, clinical pregnancy rate, ongoing 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. DiscussionThe 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. ConclusionsConventional 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.

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 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).

Recurrent spontaneous abortion (RSA) is a problem that faces women for a variety of reasons. Although leiomyomata is relatively common, calcified leiomyomata which is called “womb stones” is a very rare cause of RSA. These womb stones are correlated with retained products from conception and osseous metaplasia. We report a very rare case of a large calcified leiomyomata which caused secondary infertility and pregnancy loss of 7 pregnancies due to spontaneous abortions.

Background Our objective was to investigate the existence of an optimal period for oocyte retrieval in regards to the clinical pregnancy occurrence after the administration of recombinant human chorionic gonadotropin (rhCG) (Ovitrelle®). Methods We studied the digital records of 3362 middle eastern couples who underwent in vitro fertilization (IVF) treatment between 2019 and 2021. Results Through statistical testing, we found that there is a significant positive correlation between the oocyte retrieval period and the clinical pregnancy occurrence up to the 37th hour, where retrieval at the 37th hour was found to provide the most optimal outcome, especially in the case of gonadotropin-releasing hormone agonist (GnRHa) long protocol. Conclusions This cohort study recommends retrieval at hour 37 after ovulation triggering under the described conditions.

Objective Infertility is inadequately acknowledged as a problem in developing countries. Thyroid Autoimmunity (TAI) has been neatly investigated for its association with unfavorable pregnancy and reproductive consequences. We aim to evaluate Clinical Pregnancy Rate (CPR) as a primary outcome following In Vitro Fertilization/Intra Cytoplasmic Sperm Injection (IVF/ICSI) in women with Thyroid Autoimmunity (TAI). Methods A Retrospective cohort study included 584 women who underwent IVF/ICSI treatment between November 2012 and April 2017 in Orient Hospital, Damascus, Syria. Patients were tested for TAI before IVF/ICSI procedure. Results CPR did not significantly differ between TAI positive and TAI negative groups (p > 0.05). Subgroup analysis for only primary infertility patients showed a statistically significant difference in CPR between TAI positive and TAI negative groups. Conclusion Although several arguments were in favor of the relation between IVF/ICSI outcomes and Thyroid autoimmune disease, the presence of TAI positivity did not adversely affect the clinical pregnancy rate., Highlights • Thyroid Autoimmunity has been investigated for its association with unfavorable pregnancy and reproductive consequences. • The prevalence of TAI in Syrian women having IVF/ICSI is 25.3%. • The positivity of Thyroid Autoimmunity did not adversely affect the clinical pregnancy rate for women underwent IVF/ICSI. • Screening of Thyroid Autoimmunity constitutes a financial burden on patients more than its benefit. • The findings highlight the infertility aspects of the Syrian population.

Background: Protein C deficiency is a rare disease; it could be primary or secondary. Female patients with protein C deficiency may develop pregnancy-associated thrombosis. The clear association between the protein C deficiency and fertility or in-vitro fertilization (IVF) results has not been known yet. In our study, we aimed to determine the prevalence of protein C deficiency in Syrian infertile women and to assess the impact of protein C deficiency on abortion, recurrent IVF Failure, and IVF results.Methods: the electronic patients’ results were retrospectively screened. A total of 238 women, who had IVF cycles between January 2012 and December 2017 in a tertiary care hospital, met our including criteria.Results: the prevalence of protein C deficiency was 13.45%. There was a significant association between the protein C level and recurrent pregnancy loss (RPL). Furthermore, the protein C deficiency has an impact on the IVF results. Additionally, we did not find any association between protein C deficiency and age or number of previous IVF cycles.Conclusions: the protein C could be the hidden factor that affects IVF results. More research should be done to better understanding the role of protein C in infertility and IVF.

Endometriosis is a very common debilitating disease that occurs in 6 to 10 percent of the general female population; in women with pain, infertility, or both, the frequency is 35–50%. Endometriosis is one of the most important causes of infertility. Our objective is to evaluate the effect of endometriosis and adenomyosis on IVF outcome (ongoing pregnancy). 65 women underwent In Vitro Fertilization (IVF) and embryos transfer who had endometriosis with or without adenomyosis were recruited in this retrospective study, resulting in 53.8% had a successful IVF attempt (get pregnant). The highest success rate of IVF was in women who were in mild of endometriosis and IVF failure rate was increased mainly in women who were in severe endometriosis. So, the presence of adenomyosis affects IVF outcome and decreases the rate of implantation.

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., Highlights • Obstetric morbidities are a hallmark manifestation of antiphospholipid syndrome. • The prevalence of APS in Syrian women having IVF was less than 1%. • No correlation was found between the APA levels and age. • The APA had no impact on the IVF outcomes or the number of IVF cycles. • Screening of APA constitutes a financial burden on patients more than its benefit.

Allergic rhinitis (AR) is a common medical condition worldwide. It is an inflammation in the nasal mucosa due to allergen exposure throughout the year. Laryngopharyngeal reflux (LPR) is another medical condition that can overlap with AR. LPR can be considered an extra oesophageal manifestation of gastro-oesophageal reflux disease (GORD) or a different entity. Its diagnosis imposes a real challenge as it has a wide range of unspecific symptoms. Although AR and LPR are not life-threatening, they can severely affect the quality of life for years and cause substantial distress. Moreover, having AR is associated with having asthma which is also in turn associated with GORD. This is a cross-sectional study which used surveys distributed online on Social Media and targeted people across Syria. All participants who responded to the key questions were included. Reflux symptom index (RSI) was used for LPR, and score for allergic rhinitis (SFAR) was used for AR. Demographic questions and whether the participant had asthma were also included in the survey. We found that there was an association between the symptoms of LPR and AR p

Tobacco smoking might be impacted by various influences, including psychological, socio-cultural, and economic factors. A community-based cross-sectional survey was conducted in Syrian Arab Republic from March to April 2019 using a web-based questionnaire. The survey aimed at assessing tobacco use (shisha and cigarettes) as well as examining the association between current tobacco use and various sociodemographic and war-related factors. The sample comprised 978 participants (251 males: 727 females) and had a mean age of 24.7 years (SD: 7.60). Most participants were single (n = 825, 84.4%), reside in Damascus and Rif-Dimashq (n = 579, 59.2%), and had a college/university education (n = 911, 93.1%). Concerning smoking, a total of 371 participants (37.9%) were identified to be current tobacco smokers, of whom 211, 84, 76 were exclusive shisha smokers, exclusive cigarette smokers, and dual smokers, respectively. The prevalence of cigarette smoking (exclusive and dual) among males and females was found to be 34.7%, and 10.0%, respectively. On the other hand, the prevalence of shisha smoking (exclusive and dual) among males and females was around 34.3% and 27.6%, respectively. Additionally, various factors have predicted a higher likelihood of cigarette smoking including male gender (AOR = 4.152; 95% CI: 2.842–6.064; p

Background: Annexin A5 (ANXA5) is an abundantly and ubiquitously expressed protein showing the highest levels of concentration in kidney, liver and placenta. ANXA5 plays a central role in the machinery of membrane repair by enabling of a protective 2D bandage at membrane damaged site, has properties anti-inflammatory, pro-fibrinolytic and anti-thrombotic. Four polymorphisms have been identified in the ANXA5 promoter, which were transmitted as a joint haplotype (M2). M2 haplotype decrease the ANXA5 gene promoter activity and mRNA expression which causes several troubles.Methods: The aim of this cross-sectional study is to determine the frequency of M2/ANXA5 haplotype in healthy Syrian individuals and compare the genotype and allele distribution with other populations. In this study 94 (female, 71 and male, 23) unrelated healthy Syrian nationals were involved. 94 DNA samples have been collected in order to determine the spread the genotype M2 haplotype using allele specific polymerase chain reaction (AS-PCR).Results: Our results indicate that the distribution of the alleles and genotypes of M2 haplotype vary considerably in different populations. In the Syrian population the distribution of M2 and wide type (WT) were M2/M2 9.6%, M2/WT 44.7%, WT/WT 45.7%. The M2 haplotype was found in 45 of women (allele frequency 31%) and in 15 of men (allele frequency 32%). The distribution of the ANXA5 genotypes in Syrian study group conformed to Hardy-Weinberg equilibrium (p=0.92).Conclusions: No significant differences were found at frequency distribution of different genotypes and M2 allele between women and men within this Syrian cohort. In comparison with the results of other studies, the results of this study demonstrate that the frequency and distribution of the M2 haplotype in Syrian population are different from most other populations worldwide.

Background: The question about the role of the senior medical students in the fight against COVID-19 pandemic was raised after the serious shortage in healthcare workers faced by many healthcare systems. This research aimed to explore the ability of the final-year medical students to assist during COVID-19 in a war-torn health system.Methods: Final-year medical students in Syrian Universities were approached between 9th-17th April 2020 through an online questionnaire that assessed the students’ COVID-19-related medical knowledge (5-point score), clinical judgment (5-point score), preparedness and willingness to integrate in the healthcare facilities. An overall score of 10 points was built and multivariate analysis was conducted.Results: A total of 1764 responses were received. Valid responses were (1673) with 1199 (71.66%) responses from the final-year students. Of the latter, 728 (60.71%) scored 4 points or higher in the medical knowledge score (mean 3.69 points [SD 0.96]), while 298 (24.85%) scored 4 or higher in the clinical judgment score. Final-year students scored significantly higher than the fourth-year students in the clinical judgment score (mean 2.69 points [SD 1.12] vs 2.47 [1.15]; adjusted P=0.012). Nearly 72.4% of the final-year participants had an overall score of 7 points or more out of 10 (mean 6.39 points [SD 1.57]). Having fears of infection (log OR 0.24, 95% CI 0.05– 0.44; P=0.01) correlated with a higher overall score, contritely to beginner, intermediate English level, and male gender (log OR -0.68 [95% CI -1.01– -0.35]; PConclusion: Integrating final-year medical students may be an alternative in case of pandemics especially for fragile systems or those hit by a long-lasting war, while taking into consideration fulfilling personal protective measures, intensive training, and/or adequate supervision.

BackgroundThe Syrian crisis has entered its ninth year with many being affected by the war. This is the largest-scale study that aims to evaluate the psychological profile of secondary school students in Syria.MethodsThis is a cross-sectional study in schools in Damascus, Syria. The surveys assessed working habits, smoking, war exposure, grades, socioeconomic status (SES), social support, health-related quality of life (HRQL), post-traumatic stress disorder (PTSD), problematic anger, and other parameters.ResultsThis study included 1369 students of which 53% suffered from PTSD and 62% from problematic anger. Around 46% declared a fair or worse general health and 61% had moderate or severe mental health. Only 9.3% did not report exposure to any war-related variable. War exposure had an impact on PTSD, anger, and HRQL, but not on students' grades. Smoking, having consanguineous parents, and working did not have a clear association with grades or anger. Social support weakly reduced PTSD and anger scores. Interestingly, working was associatedwith lowerPTSD scores but was associated with a worse physical component of HRQL.ConclusionThis is the largest study on school students in Syria that reports the psychological ramifications of war. Although the direct effects of war could not be precisely described, the high burden of PTSD and anger distress was a strong reflection of the chronic mental distress.

ObjectivesTo demonstrate the burden of laryngopharyngeal reflux (LPR) in Syria and its associated variables.DesignThis is a cross-sectional study that used online questionnaires that included demographics, smoking, war-related questions and reflux symptom index (RSI).SettingThis research was conducted online across Syria and included the general population.ParticipantsParticipants who lived in Syria, agreed to participate, and responded to all the RSI questions were included. This research comprised 734 participants, with 94.6% response rate, 75.5% being females, and a mean age of 24 years.ResultsOverall, 31.9% of subjects had symptoms suggestive of LPR. Participants who were 30 years and younger had fewer symptoms suggestive of LPR compared with the older group p=0.012 (OR 0.534; 95% CI 0.325 to 0.877). While having an epigastric burning sensation, chest pain and indigestion were the most common symptoms, having a sore throat was the least common. Being distressed from war noises was associated with more symptoms p=0.009 (OR 1.562; 95% CI 1.117 to 2.183). However, losing someone or changing place of living due to war were not significantly associated with these symptoms p>0.05. RSI scores were associated with cigarette and/or shisha smoking pConclusionsWar, smoking, asthma, allergies, respiratory conditions and having a job were associated with LPR symptoms. However, they may be associated with these symptoms independently from LPR; for instance, similar symptoms can be caused by the mental disorders from war, the unique environment and irritant substances of the laryngeal mucosa.

Backgrounds: Syria has entered its ninth year of conflict and as its medical sector facing major hurdles, laryngopharyngeal reflux (LPR) is often overlooked although it has an association with worsening quality of life and affecting many aspects as it is chronic and left untreated although it can lead to many complications such as dysphonia. This study is to evaluate LPR prevalence and its association with different aspects such as cigarette, and shisha smoking, and the effect of war on LPR.Methods: Cross-sectional study by using online questionnaires that included demographics, smoking, war related questions and reflux symptom index (RSI) were used online in many cities around Syria.Findings: This research included 734 responders with 75.5% being female and the mean age being 23.97 years. 31.9% of subjects had symptoms suggestive of LPR. Participants were Syrians and we included every responder who agreed and did not neglect any question. We only found that being distressed from war noises was associated with positive LPR symptoms [P=0.009 (OR, 1.562; 95% CI 1.117-2.183)], but losing someone or changing place of living due to war were not associated with LPR. LPR was associated with cigarette smoking (PInterpretations: About one third had LPR symptoms. War distress from war noise, cigarette smoking, asthma, and allergic were significantly correlated with LPR.

Allergic rhinitis (AR) is a very common medical condition worldwide which affects the quality of life of many for long periods throughout the year. It has many symptoms such as sneezing, a sore throat, globus pharyngeus, rhinorrhoea, congestion, and postnasal drip that may overlap with laryngopharyngeal reflux (LPR) which is a different medical condition. LPR can be considered as an extra oesophageal manifestation of gastro-oesophageal reflux disease (GORD) or a different entity altogether. LPR can go under-diagnosed as there is no definitive diagnostic tool. LPR can impose a real challenge as it may occur for years without diagnosis which can affect the quality of life even more. Having AR can also increase the chance of having asthma which is also in turn correlated with having GORD. Although AR and LPR are not life-threatening, they are persistent medical conditions, meaning they affect the everyday life and causing unnecessary distress. In this study we evaluate their correlation in Syria in the Middle East as there are not many studies on this topic. We found responders with LPR symptoms do have more AR symptoms (P

The Syrian crisis has entered its tenth year with incessant conflicts in many locations across Syria. Much of the population have been impacted including children who suffer the direct and indirect war effects of war. To date there has been no large scale study examining the mental health and academic impacts of the war of children in Syria. This large-scale cross-sectional study aims to evaluate the psychological profile of school students in Damascus Syria examining PTSD, anger and general mental health and examine their relationships with work, smoking and academic performance. The study included 1369 students from seven different schools. Surveys included assessment of mental and physical well-being using a measure of health related quality of life (SF8), Posttraumatic stress disorder (CRIES-13), problematic anger (DAR5) smoking, working habits, social support and academic grades. The study found that more than half of the children suffered from PTSD (53%), problematic anger (62%) with this being associated with poorer SF-8 (quality of life) scores in both mental and physical domains and more time watching TV and Internet. Around 46% declared fair or worse general health and 61% having moderate or severe mental health. War variables had an impact on PTSD, anger, and SF-8, but not an impact on grades. Worse HRQL was associated with war variables and smoking. Social support was negatively correlated with SF-8, PTSD, DAR-5 anger and declarations of close friends being the main source of support. This is the largest study of children is Syria to date that reports on the psychological ramification of war. The study demonstrates the severe impact on children across both mental health and physical health. Although direct war effect could not be observed, the high burden of PTSD and anger distress is a strong reflection of the chronic mental trauma. School students have had to work and face many hurdles in a young age which has left them severely impacted.

Background. Allergic rhinitis (AR) is a global disease that affects a huge proportion of people around the world especially in the Middle East, where multiple allergy-promoting factors can be found. Although AR is not fatal, it severely affects the quality of life. However, it is usually overlooked in developing countries due to resource scarcity. Methods. An online questionnaire on social media was used which included demographics, smoking, socioeconomic-status (SES), war-related questions, and the score for allergic rhinitis (SFAR), a simple self-reporting tool with the cut-off point at 7. Findings. This study included 968 subjects with 721 (74.5%) females. The mean age was 24.69 years with AR prevalence at 47.9%. AR was associated with male gender [P=0.001 (OR, 1.677; 95% CI 1.249-2.253)], having a job [P=0.049 (OR, 1.309; 95% CI 1.001-1.713)], the having a chronic medical condition (P<0.0001) mainly other allergies [P<0.0001 (OR, 9.199; 95% CI 3.836-22.063)] and asthma [P=0.006 (OR, 5.060; 95% CI 1.396-18.342)], using medications (P<0.0001) and living in particular provinces (P=0.010). However, no significant correlation was found with type of work and war factors except being distressed by war sounds [P=0.027 (OR, 1.348; 95% CI 1.034-1.757)]. Finally, no associations were found with age, consanguinity, SES, educational level, and cigarette or/and shisha smoking (P>0.05). Interpretation. Approximately half of the sample displayed AR symptoms, indicating a potentially high burden of AR in the community. A correlation to being distressed from war noises was found with AR which could reflect a psychological aspect. In addition, in war harmful allergens are released which can be an additional AR risk factor which adds to the environment in the Middle East that is associated with AR. However, we need further studies to discover and minimize this huge prevalence of AR.

Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer and has a high survival rate when properly managed. Prognosis is correlated with many factors such as age, gender, white blood cell (WBC) count, CD10, French-American-British (FAB) classification, and many others. Many of these factors are included in this study as they play a major role in establishing the best treatment protocol. This study aims to demonstrate clinical and laboratory features of childhood ALL in Syria. They were treated at Children’s University Hospital, the only working major cancer centre in Syria at the time of the study. Data of 203 patients who aged 0–14 years were obtained for this study. Most patients (48.8%) aged (5–9) years with a male predominance (60.9%). The major features for ALL included lymphadenopathy (82.9%), presenting with systemic symptoms (74.9%), T-ALL subclass (20.2%), L2 FAB classification (36.1%), low educational levels for fathers (53%) and mothers (56.2%), having a high risk (48.4%), and having a duration of symptoms before evaluation for more than 4 weeks (42.6%). Only three (1.5%) patients had normal full blood counts (FBC) and only one (0.5%) patient had an isolated high WBC count at time of presentation. Most patients had either abnormal platelet count (89.3%) or low haemoglobin level (88.8%) when presenting with only (2.0%) having normal levels for both. This suggests that having normal haemoglobin and platelet count can be used for quick screening in crisis time like in Syria for prioritising patients. Many prognostic factors were significantly different from medical literature which emphasises the importance of local studies in the developping countries. This study included a high prevalence of T-all, L2 FAB classification, high-risk and other variables which require further studies to evaluate the aetiology of these features, especially that treatment protocols may have a higher mortality in developing countries when not adjusted to local variables.

Introduction: Gynaecological complaints and primary dysmenorrhoea among young females are usually managed using popular myths, and have a wide spectrum of consequences on everyday life. Methods: A cross-sectional study to assess the prevalence of dysmenorrhea and basic knowledge, with a pre-post analysis after the intervention was applied. The study was carried in randomly selected female public schools in Damascus on a randomly selected sample of female students aging between 10 and 18 years old. We used a self-report questionnaire immediately before the awareness sessions and two weeks later. The questionnaire included multiple-choice questions on various aspects of the menstrual cycle, dysmenorrhoea and common myths in the Syrian society. The data were analyzed using SPSS ® , Microsoft Excel ® , and Microsoft Access ® software. Results: A total of 579 vs. 261 female students participated. The prevalence of dysmenorrhoea was 87.2%. Only 47.3% of participants knew the correct origin of menstruation blood, and most of them did not consult a doctor regarding the pain (91.6%). The answers were weighed and compared, resulting in an insignificant p-value for the students’ knowledge after the awareness campaign (p = 0.687, CI = 95%). Discussion and conclusion: Dysmenorrhoea is highly prevalent among Syrian school students. The modest knowledge on this condition, the use of home remedies and the insignificant improvement after the sessions indicate the need to focus on creatively improving information delivery methods in a long sustainable timeframe.