Characterization and risk factors for unexplained female infertility in Sudan:A case-control study

BACKGROUND Female infertility with unknown causes(unexplained)remains one of the mysteries in the reproductive health field,where the diagnostic evidence is still weak and the proposed treatments still work with unknown methods.However,several studies have proposed some possible causes and risk factors for unexplained female infertility.AIM To characterize and identify factors associated with unexplained infertility in Sudanese women.METHODS A matched(age and body mass index)case-control study was conducted from March 2021 to February 2022.The study samples were 210 women with unexplained infertility(UI)and 190 fertile women of reproductive age who were attending the maternity hospitals and fertility clinics in Khartoum,Sudan.The risk factors of unexplained infertility were identified using a structured,pretested questionnaire containing information on socio-demographic variables,anthropometrics,clinical diagnosis of infertility,behavioral factors,physical activity assessment,diversity,and consumption of different food groups by the study participants.RESULTS The results showed a higher proportion of women diagnosed with UI were residents of rural areas than controls(21.4%vs 11.1%,P<0.05),and previous miscarriages and/or abortions were more common in fertile women compared with infertile women(13.16%vs 5.71%,P<0.05).Additionally,infertile women had a significantly(P<0.05)higher proportion of family history of infertility(explained and unexplained)compared with controls.Finally,after controlling for the effects of potentially confounding variables using multivariable logistic regression analysis,only marital status,family history of infertility,use of modern contraceptives,smoking,caffeine consumption,physical activity level,meals consumed,other vitamin-A-rich fruits and vegetables,and other vegetables were found to be significant(P<0.05)factors associated with unexplained infertility among Sudanese women.CONCLUSION Married women with a family history of infertility who smoke and consume a high amount of caffeine,who live a sedentary lifestyle,and who consume more than two meals free of vitamin-Arich fruits and/or vegetables and/or other vegetables per day are at the highest risk of developing unexplained infertility.

Fertilization of IVF/ICSI Using Sibling Oocytes from Couples with Subfertile Male or Unexplained Infertility

The significance of the performance of conventional in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) using sibling oocytes from couples with subfertile male or unexplained infertility was evaluated. A total of 410 sibling oocyte cumulus-corona complexes (OCCC) from 21 couples with subfertile male (group A) and 11 unexplained infertile couples (group B) were randomly divided, in order of retrieval, into two groups inseminated either by conventional IVF or by ICSI. The treatment outcomes and the influence of infertility factors on fertilization in each group were compared. The results showed that although the two pronuclear (2PN) fertilization rate per injected sibling oocytes was significantly higher after ICSI (group A: 68.2 %±28.8 %; group B: 66.2 %±24.9 %) than after conventional IVF (group A: 41.8 %±32.7 %; group B: 40.1 %±22.1 %), the other variables studied included: the fertilization rates of per allocated sibling oocytes IVF/ICSI, the fertilization rates of sibling oocytes IVF/ICSI after excluding failed IVF fertilization cycles, as well as the cleavage rates of normal fertilization were not statistically significant (P>0.05). Similarly, though the total fertilization failure rate in the IVF group (group A: 42.9 %; group B: 36.4 %) was significantly higher than in the ICSI group (group A: 4.8 %; group B: 0), we did not cancel cycles due to the normal fertilization of sibling oocytes. Embryo transfer was possible in all 32 couples. There were 10 clinical pregnancies in the two groups. We also discovered a possible association between some semen parameters and sperm functions of group A, and women age and duration of infertility of group B and fertilization. It is suggested that adoption of the split IVF/ICSI technology in the above cases may help eliminate fertilization failures. This is also a useful method to investigate the effect of single factor on the employment of assisted reproductive technology.

Unexplained abdominal pain due to a fish bone penetrating the gastric antrum and migrating into the neck of the pancreas: A case report

BACKGROUND Ingestion of foreign bodies results in gastrointestinal perforation in approximately 1% of patients,and fish bones are the objects that most commonly lead to bowel perforation. When it does occur,the terminal ileum is the most common site of perforation,followed by the duodenal C-loop. However,involvement of the pancreas is very rare. Because clinical symptoms are nonspecific and gastrointestinal perforation may present as only odynophagia or abdominal pain,a definite preoperative diagnosis and clinical intervention may be delayed.CASE SUMMARY We report the case of a 32-year-old man who presented to our hospital because of abdominal pain that had worsened over 5 d. He had no significant past history except that he had eaten fish 1 wk previously. Upper endoscopy revealed an irregular submucosal tumor on the front wall of the gastric antrum. Endoscopic ultrasonography and computed tomography showed a fish bone penetrating the gastric antrum and migratingin to the neck of the pancreas. The patient underwent laparoscopic surgery and had no complications one week after the operation.CONCLUSION A recent history of foreign body ingestion and imaging examinations are helpful for diagnosis of unexplained abdominal pain caused by foreign bodies.

Leptin levels in women with unexplained infertility:A systematic review and meta-analysis

BACKGROUND Unexplained infertility(UI)is usually used for any heterosexual couple who failed to have a successful clinical pregnancy without identifying clear causes after they undergo all standard fertility tests.Evidence shows that leptin is one of the most accurate biomarkers for UI.Nevertheless,conflicting results regarding leptin levels in women with UI have been reported.AIM To find the serum leptin levels in women with UI.METHODS All studies written in English and conducted before April 30,2021 from PubMed/MEDLINE,Embase,Cochrane Central Register of Controlled Trials,ClinicalTrials.gov,Google Scholar,OpenGrey,OATD,and the infertility conference abstract were included.Studies were found eligible if they provided the mean and standard deviation of leptin for the case group and control group.The quality assessment of individual studies was evaluated using the Joanna Briggs Institute Quality Assessment Tool.Data synthesis and statistical analysis were done using STATA software version 16.RESULTS A total of 378 studies were reviewed,and just six studies that fulfilled the eligibility criteria were included in this meta-analysis.The pooled result showed that leptin levels were significantly higher in women with UI compared to fertile women,with a standardized mean difference of 0.97(95%confidence interval:-0.49-2.43).However,heterogeneity across studies was highly significant(P<0.00001;I2=98.8%).CONCLUSION The results of this study suggest that leptin levels are elevated in women with UI compared with fertile women;hence,leptin could be a potential biomarker for UI in women,and it may be useful for identifying women with a high risk of infertility.

Research advances of Chinese and Western medicine in the treatment of unexplained recurrent spontaneous abortion

Recurrent spontaneous abortion is a common disease in gynecology,and it seriously affects women's reproductive health and brings heavy burden and pain to society and families.The cause of recurrent spontaneous abortion is complicated,in addition to the well-defined genetic,anatomical,infection and endocrine factors,and there are still some unknown causes,which is called as unexplained recurrent spontaneous abortion,accounting for 40%of recurrent abortion.At present,there are a lot of researches on the treatment methods of the patients with the unexplained recurrent spontaneous abortion,which also shows that the treatment of traditional Chinese and Western medicine all have certain clinical application effect.Western medicine clinical methods mainly includes immunotherapy,immunosuppressive therapy,anticoagulation therapy,progesterone therapy,etc.Based on the experience of the professor and combined with many years of clinical practice,the author believes that the pathogenesis of this disease in traditional Chinese medicine is mainly due to impaired impulse and deficiency of Spleen,lack of qi and blood,can not nourishing the fetus;deficiency of Kidney Qi,blood flow was delayed,and blood stasis and could not raise the fetus.Clinical treatment is based on invigorating the kidney,tonifying spleen and nourishing blood,promoting blood circulation to remove blood stasis and dredging collaterals.Oral Chinese medicine combined with external acupuncture and moxibustion has achieved excellent effects in improving pregnancy rate.This article reviews the domestic and foreign methods of treating unexplained recurrent miscarriage in order to provide clinical reference.In the future,the combination of Chinese and Western medicine should become the main therapy to increase pregnancy rate.

Endometrial Injury and Sub Endometrial Doppler Study to Predict Uterine Receptivity in Women with Unexplained Infertility: A Randomized Controlled Trial

Objectives: The aim of this work was to compare the effectiveness and safety of endometrial scratching at different times of the menstrual cycle on cumulative pregnancy rate and also to assess and clarify its relationship and effect on sub-endometrial vasculature blood flow by Doppler ultrasound, in cases of unexplained infertility attempting to conceive spontaneously (without ovulation induction). Study Design: A prospective randomized clinical control study. Patients and Methods: A total of 252 eligible participants were included in the study and randomly allocated using block randomization into three groups: Group A (n = 84): endometrial scratching was performed during the pre-ovulatory days and Group B (n = 84): endometrial scratching has been done at day 7 of the cycle. Group C (control group): includes 84 cases without endometrial scratching. The Doppler ultrasound will be done. The pulsatility index (PI) and resistance index (RI) of endometrial and sub endometrial arteries were calculated. All women were followed up to 3 months. Results: Cumulative pregnancy rate is 21.42% and 28.57% in the study groups A and B respectively which is higher than group C (control group) (4.76%) but with statistically insignificant P-value = 0.254. There is statistically significant difference in RI & PI between the studied groups and the control group on day 13 (P value < 0.001). There is statistically significant difference in PI between day 13 and day 6 for the same group in both groups (A&B) (P value < 0.003), while there is no statistically significant difference in Group C (P value = 0.156). Conclusion: Endometrial scratching is a cost-effective and easy technique which may improve clinical pregnancy rates and endometrial blood flow in women with unexplained infertility.

Clinical pregnancy rate of women with unexplained infertility with or without cervical mucus aspiration before intrauterine insemination: A randomized controlled trial

Objective:To detect effect of removing cervical mucus before performing intrauterine insemination(IUI)on pregnancy rate in patients with unexplained infertility.Methods:The randomized controlled trial was conducted in Infertility Division of Department of Obstetrics and Gynaecology of a tertiary care hospital.Totally 80 patients of unexplained infertility were recruited.By computer generated block randomization in block size of 4 and 6,patients were randomly allocated at time of starting ovarian stimulation into the cervical mucus removal group or the non-removal of cervical mucus group before IUI,40 in each group.Ovarian stimulation with clomiphene 100 mg from day 2-6 of menstrual cycle along with human menopausal gonadotropin 150 IU was given alternate day starting from day 7.Follicular monitoring was done and further doses given as per response;trigger was planned when 1-3 follicle reach a diameter of>18 mm.IUI was planned after trigger.IUI was done as per the group allocated.Mucus cleaning was done in the cervical mucus removal group by aspirating mucus with IUI syringe and sterile cotton swab before IUI.The primary outcome was clinical pregnancy rate.Number of difficult IUIs and cycle cancellation due to ovarian hyperstimulation were also noted.Results:IUI was not done in 4 patients due to hyperstimulation.Pregnancies per IUI cycle occurred in 7.9%(3/38)in the cervical mucus removal group and 21.1%(8/38)in the non-removal of cervical mucus group.There was no statistically significant difference in clinical pregnancy rate between two groups(P=0.19).Conclusions:There is a trend towards a lower clinical pregnancy rate with removal of cervical mucus before IUI in women of unexplained infertility though the difference is not statistically significant.Further studies with large sample size need to be done on this intervention.

Expression of AIF-1 and RANTES in Unexplained Spontaneous Abortion and Possible Association with Alloimmune Abortion

Objective To investigate the effects of allograft inflammatory factor-1 （AIF-1） and （RANTES） in sera and deciduas on unexplained early spontaneous abortion. Methods AIF-1 and RANTES were examined in sera and deciduas/endometria of 43 unexplained early spontaneous abortion women （group A）, 40 healthy women with early pregnancy（group B） and 20 healthy women with no pregnancy （group C）. Immunohistochemistry and enzyme linked immunosorbent assay （ELISA） were used in this study. Results AIF-1 protein was expressed both in deciduas of group A and in endometria of group C. In group A, H scores in the recurrent abortion deciduas specimens were significantly greater than those in the first abortion;in endometrium, expression of AIF-1 was greater in the secretory than in proliferative phase of group C. In group B, concentrations of RANTES in sera were higher in 7th-8th week of pregnancy than in 6th-7th and 〉8th week of pregnancy; expression of AIF-1 protein showed a negative correlation with RASNTES concentration; a significant increase of the RANTES levels in sera and tissue was observed in group B. Conclusion These results demonstrate, for the first time, that AIF-1 are expressed in deciduas of unexplained spontaneous abortion suggesting that AIF-1 involve in alloimmune abortion; RANTES might act as a novel blocking antibody;AIF-1 and RANTES might act as reliable markers for diagnosis of early alloimmune abortion.

Evaluation of Steroid Receptors mRNA Fingerprints in Two Groups of Normozoospermic Patients: Men from Unexplained Infertility Couples vs. Men from Couples with Tubal Factor Infertility

The study of sperm cellular components at molecular level is crucial for the diagnosis of male unexplained infertility. The aim of the study was to compare the molecular profile of steroid receptors and aromatase in spermatozoa obtained from two normozoospermic groups of patients issued from couples treated for infertility. We investigated 46 male patients from unexplained infertility couples and from men, 38 where female partners presented with tubal infertility. Sperm ERs (estrogen receptors: alpha and beta), GPER (G protein-coupled estrogen receptor), AR (androgen receptor) and aromatase mRNA expression levels by TaqMan qPCR were analyzed. AR transcript level was significantly lower in sperm of men from unexplained infertility couples vs. men from couples with tubal factor infertility (P = 0.04). Although the AR mRNA expression level did not had any effect on embryo development and its implantation, a significant correlation between AR mRNA levels and clinical pregnancy in unexplained infertility patients was observed. Taken together, AR transcript presence in ejaculated spermatozoa could be a potential marker for unexplained infertility.

Medically Unexplained Symptoms (MUS): What Do Current Trainee Psychologists, Neurologists and Psychiatrists Believe?

Objectives: Medically unexplained symptoms (MUS) are common in all medical settings. These conditions remain controversial, aetiology remains poorly understood and treatments have been slow to develop. This study aimed to examine the beliefs held by psychologists and other professionals about MUS, which may impact upon clinical practice. Design: 375 clinical psychology trainees from 23UKtraining courses, 12 neurologists and 19 psychiatrists in training completed a weblink survey designed to elicit a range of beliefs about MUS cause and treatment. Results: All three groups viewed MUS as a common clinical problem. Use of terminology differed between groups. All three groups held a view that sexual abuse was a medium to high risk factor for developing MUS. Only a minority of psychologists and psychiatrists doubted that the human mind is capable of massive repression for past distressing events;and few psychologists, and no psychiatrists, doubted the traditional psychodynamic causal model of MUS. Neurologists were generally more skeptical. Only a minority of all three groups disagreed that hypnosis was a helpful way to uncover memories that people can not access. Around one third of each group believed that traumatic memories recovered in therapy were reliable. Dualistic thinking was prevalent among all three groups, but more so among psychiatrists. Conclusions: The data show that many professsionals hold beliefs about MUS for which, empirical support is lacking. These beliefs may impact on clinical practice. Whether such beliefs are deemed to be correct or incorrect, they should be acknowledged.

Treatment of Unexplained Infertility by Acupuncture in Natural and Control Ovarian Hyperstimulation Cycles: A Prospective Analysis

Acupuncture is an important method of treatment in Chinese medicine. The objective of this study was to evaluate the efficacy of acupuncture as an adjuvant treatment for unexplained infertility. Here we conducted a prospective study, with data consisting of acupuncture group (38 cases) and control group (42 cases). Infertility evaluation workup consisted of semen analysis, ovulation assessment, hysterosalpingogram (HSG) and blood analysis. The patients in acupuncture group received 3 acupuncture sessions, and each at seven acupuncture points (EX-CA1, CV4, CV6, SP10, ST36, SP6, and KI3). The session started 12 days before menstruation and continued for 10 days. The patients in control group did not receive acupuncture. All patients tried 1 - 3 natural cycles 3 months after HSG test, if not pregnant, underwent 1 - 3 cycles of control ovarian hyperstimulation (COH) and timed intercourse. Pregnancy was evaluated by measurement of blood β human chorionic gonadotrophin (β-hCG) and subsequent trans-vaginal ultrasound. No significant difference of clinical pregnancy rate was found between the acupuncture group and the control group, however, numbers of COH cycles were significantly less and more pregnancies occurred in natural cycle in the acupuncture group. We concluded that acupuncture can be used as an adjuvant treatment for unexplained infertility. Although acupuncture did not increase the cumulative pregnancy rate, it decreased the number of COH cycles and more patients got pregnant in natural cycles after receiving acupuncture.

Laparoscopy and the Era of ART in Unexplained Primary Infertility: Randomized Clinical Trial

OBJECTIVES: To compare the outcomes (effectiveness and safety) of laparoscopic surgery as a treatment option of unexplained primary infertil-ity with ART. DESIGN: Randomized prospective clinical trial. PATIENTS AND METHODS: 536 patients with primary unexplained infertility diag-nosed by normal hormonal profile and ovulatory at ovulation testing, nor-mal HSG, and normal semen analysis were randomized according to com-puter based system into: group I, 267 patients were managed with laparos-copy with aim of diagnosis and treatment. While in group II, 269 patients were treated by controlled ovarian stimulation and IUI up to 3 trials, if failed ICSI was performed. We calculated cumulative pregnancy outcome after two years for each group. RESULTS: In group I, Laparoscopic find-ings were as follow: minimal to mild endometriosis was found in 83 cases (31.1%), moderate to severe endometriosis 44 cases (16.5%) managed by adhesiolysis and ablation-excision of endometriotic implants. The preg-nancy rate after two years was 55.4% (46 cases), 38.6% (17 cases) in both respectively, significant periadnexal and pelvic adhesions 41 cases (15.3%) managed by adhesiolysis with pregnancy occurred in 22 cases (53.7%), while laparoscopy revealed hypo plastic tubes 33 cases (12.4%), and 66 cases (24.6%) remained unexplained. With the expectant manage-ment, pregnancy rate was 21.2% (7 cases), and 15.2% (10 cases) respec-tively. The overall pregnancy rate in group I is 102 cases (38.2%). In group II, 114 cases (42.3) got pregnant as 27 cases (8.78%) by IUI, and 87 cases (33.52%) by ICSI. OHSS occurred in 3 cases, multiple pregnancy occurred in 13 cases, abortion and miscarriage 6 cases in group II, while 2 cases of ectopic pregnancy in group I, and the patients of both groups did not suffer any significant operative complications. CONCLUSION: Laparoscopy is safe and effective as a treatment option in unexplained infertility and its performance provides diagnostic findings which are valuable in manage-ment of the unidentified causes, enabling good number of patients to have pregnancy spontaneously which is comparable to ART while avoiding economic, psychological and physical burdens of ART, like OHSS, multi-ple pregnancy and abortion which are higher in cases treated with ART. In the future if ART is needed, the success rate is increased by closure of (undiagnosed) hydrosalpinx and reposition of the ovary to facilitate oocyte retrieval.

Timed Intercourse versus Intrauterine Insemination with Mild Ovarian Stimulation for Unexplained Infertility

Background: Infertility is unexplained in about 22% - 28% of infertile couples. Spontaneous pregnancy may occur in them. If did not happen, Expectant management will be via clomiphene citrate (CC) administration, intrauterine insemination (IUI), and IVF & ICSI. Aim: to assess the effectiveness of intrauterine insemination with mild controlled ovarian stimulation compared with expectant management in couples with unexplained infertility more than one year. Methods: 160 couples with unexplained infertility were selected, The couples were randomly divided into two groups: Group (A) “80 couples”: Intrauterine insemination (IUI) with mild controlled ovarian stimulation (combination of CC + hMG) using prepared semen and was performed 36 hours after hCG injection, Group (B) “80 couples”: Couples had no ovulation induction. They encouraged for timed intercourse in the most fertile days of female cycle guided by folliculometry for 6 months. Data were collected quantitatively, coded and analyzed using SPSS. The power of study is 80% and 95% confidence interval. Result: The pregnancy rate was calculated in both groups: In group (A) (IUI/COS): OPR (Ongoing pregnancy rates) was 27.5% and PR (pregnancy rates)/cycle was 8.6%. In group (B) (Expectant management): OPR was 25% and PR/cycle was 5.3%. Conclusion: Mild controlled ovarian stimulation CC + hMG with IUI offers no statistical significance in terms of pregnancy outcomes over expectant management in this study however significance in the response to stimulation.

Serum leptin level in Sudanese women with unexplained infertility and its relationship with some reproductive hormones

BACKGROUND The excessive concentration of leptin has negative effects on all aspects of female reproduction.Despite this established relationship,the exact role of leptin in women’s fertility is not clear enough and needs more clarification.AIM To evaluate the serum leptin levels in Sudanese women and to ascertain the relationship between serum leptin levels and unexplained infertility(UI).METHODS A matched(age and body mass index)case-control study was conducted from March 2021 to February 2022.The study samples were 210 women with UI and 190 fertile women of reproductive age who were attending the maternity hospitals and fertility clinics in Khartoum state Sudan.The serum concentration of leptin and other serum biomarkers were determined using enzyme-linked immunosorbent assays.RESULTS The results showed that there was a highly statistically significant difference between the two groups(P<0.001)for all examined eight biomarkers.Whereby,leptin,luteinizing hormone(LH)/follicular stimulating hormone(FSH)ratio,prolactin hormone(PRL)and testosterone(T)were significantly higher in the UI group compared with the control group.In contrast,FSH and estradiol(E2)/T ratio were significantly lower in the UI group than in the control group and the effect size test for the difference between the two groups was very large(effect size>0.80),for leptin level,LH/FSH ratio,PRL level,and E2/T ratio,and large(effect size 0.50-≤0.80)for FSH and T.CONCLUSION This study reveals that leptin could be a potential biomarker for UI in Sudanese women and it may be useful for identifying women with a high risk of infertility.

Methylene Tetra-Hydrofolate Reductase Gene Polymorphism and Endometrial Perfusion in Unexplained Female Infertility

Aim of the study: Examing the role of Methylene tetra-hydrofolate reductase (MTHFR C677T) polymorphisms in unexplained female infertility. Methods: The study was conducted on women with unexplained infertility attending the Infertility Clinic at El-Shatby University Hospital, Alexandria, during the period from October 2020 to October 2021. Uterine artery Doppler assessment and detection of MTHFR C677T gene mutation were done. The frequencies of homozygous and heterozygous gene mutations were determined. Results: In group I, 35 cases had abnormal uterine artery Doppler compared to 22 normal cases in group II. As regards MTHFR C677T gene mutation, 19 cases were positive in group I (7 were homozygous and 12 were heterozygous) and only one case was positive in group II (heterozygous) which was statistically significant. Conclusion: MTHFR C677T gene polymorphisms may play a role in unexplained infertility.

Antioxidant Supplement Improves the Pregnancy Rate in Patients Undergoing in Vitro Fertilization for Unexplained Infertility

Objective: This is a retrospective study to evaluate the effect of using the antioxidants containing coenzyme Q10 (CoQ10) and omega-3 in patients undergoing in vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI) for unexplained infertility. Materials Methods: A total of 299 patients undergoing IVF-ICSI for unexplained infertility at the IVF center of Ondokuz Mayis University were studied. The subject group consisted of 135 patients who used OMEPA Q10 (Co Q10 100 mg, omega-3 600 mg, eicosapentaenoic acid 300 mg, docosahexaenoic acid 230 mg) for two months before ovarian stimulation. A group of 164 patients who did not use the supplement were evaluated as the control group. Results: The pregnancy rate of patients using antioxidants was statistically higher than that of those who did not use the supplement (p 0.05). The pregnancy rates of patients in the two groups were 32.9% and 49.6% respectively. The pregnancy rate of patients using antioxidants was statistically higher than that of those who did not use the supplement (p 0.05) seemed not enough. Conclusion: We concluded that using antioxidants that contain Co Q10 and omega-3 in patients undergoing IVF-ICSI for unexplained infertility increased the clinical pregnancy rate. We recommend using antioxidants that contain Co Q10 and omega-3 in infertile patients.

A multi-center study of hemodynamic characteristics exhibited by children with unexplained syncope

Background Syncope is common in children and adolescents, with 15% estimated to have had at least one syncopal episode by age 18. In recent years, an increasing number of children, especially girls at their school age, have developed unexplained syncope. The mechanism of an unexplained syncope exhibited by children is incompletely studied; the association between different hemodynamic patterns and clinical features is also not clear. The aim of the study was to investigate the hemodynamic patterns of children with unexplained syncope and to examine the clinical relevance. Methods Two hundred and eight children [87 boys, 121 girls, aged 3-19 years, mean （11.66±2.72） years] were selectively recruited from May 2000 to April 2006 when they presented syncope as their main complaint at the Multi-center Network for Childhood Syncope in Beijing, Hunan Province, Hubei Province, and Shanghai of China. All of the patients underwent head-up tilt tests; data were analyzed using SPSS version 10.0 for Windows. Continuous variables were expressed as the mean± standard deviation. Dichotomous variables were compared through a X^2 test. A value of P〈0.05 （two sided） was regarded as statistically significant. Results The age distribution of children with syncope was approximately normal. Head-up tilt tests was positive in 155 children, and the incidence of positive response of the baseline head-up tilt test for diagnosing unexplained syncope was 50.48%. The sensitivity value and diagnostic value of sublingual nitroglycerin head-up tilt test were both 74.52%. The hemodynamic pattern was normal in 53 children. The 155 children, who were positive in head-up tilt tests, showed signs of postural orthostatic tachycardia syndrome （60, 28.8%）, the vasoinhibitory pattern （72, 34.6%）, the cardioinhibitory pattern （5, 2.4%）, and the mixed pattern （18, 8.7%）. The gender distribution between the two age groups （age 〈 12 years vs age ≥ 12 years） was not different （P〉0.05）. The distribution of hemodynamic patterns between the children of the two age groups （age 〈 12 years vs age ≥ 12 years）, and the children with different complaints （dizziness vs syncope） was significantly different （P〈0.05）, while the distribution between the children of different sexes and different lasting time of syncope （≤ 5 minutes vs 〉 5 minutes） was not significantly different （P〉0.05）. Different hemodynamic patterns were differentiated by differing syncope inducements, presymptoms, and complicated symptoms during and after syncope. Conclusion The tested girls were more prone when compared with the boys to have unexplained syncope, and the peak age was around twelve years old. The incidence of positive response of head-up tilt tests was also relatively higher for the girls. The distribution of hemodynamic patterns for different ages was different. For children with unexplained syncope, we should use head-up tilttests to distinguish the hemodynamic patterns in order to adopt rational therapeutic measures.

Role of cyclooxygenase-2 signaling pathway dysfunction in unexplained recurrent spontaneous abortion

Background Experimental evidence indicates that cyclooxygenase-2 （COX-2） plays a critical role in blastocyst implantation; however, little is known of the role of COX-2 in unexplained recurrent spontaneous abortion （URSA）. Methods We evaluated the expression level and potential signaling pathway of COX-2 in 30 cases of URSA who were excluded the abnormality of chromosomes, anatomy, endocrine, infectious, autoimmune diseases and in 30 normal pregnancies. Results The mRNA and the protein expression level of COX-2 in the URSA group （-0.238±0.848, 0.368±0.089, respectively） were significantly lower than that in the control group （1.943±3.845, 1.046±0.108, respectively） （both, P 〈0.01）. The expression of prostaglandins PGF2a, PGD2, PGE2, and PGI2, in the URSA group （（2326.0±295.6） pg/ml, （2164.0±240.5） pg/ml, （238.7±26.4） pg/ml, （2337.0±263.0） pg/ml, respectively） were significantly lower than that in the control group （（3450.0±421.7） pg/ml, （3174.0±415.6） pg/ml, （323.5±43.8） pg/ml, （3623.0±460.4） pg/ml, respectively） （P 〈0.05）. The mRNA expression level of PPARI3 and RXRa （0.859±0.653, -0.172±0.752, respectively） in URSA group was significantly lower than that in the control group （1.554±1.735, 0.777±2.482, respectively） （both P 〈0.05）. The mRNA and protein expression levels of vascular endothelial growth factor-A （VEGF-A） in the URSA group （2.010±1.522, 0.35±0.46） was significantly lower than that in the control group （4.569±2.430, 0.750±0.350） （both P 〈0.05）. Conclusions COX-2 and the COX-2-derived PGI2 signaling pathway possibly play an important role in successful embryo implantation, and their decreased expression may result in URSA. The decreased expression may influence the expression of VEGF-A which interferes with placental angiogenesis causing failure of embryo implantation, leading to spontaneous abortion.

In vitro fertilization-embryo transfer in patients with unexplained recurrent pregnancy loss

Background:Empiric therapy for patients with unexplained recurrent pregnancy loss(URPL)is not precise.Some patients will ask for assisted reproductive technology due to secondary infertility or advanced maternal age.The clinical outcomes of URPL patients who have undergonein vitro fertilization-embryo transfer(IVF-ET)require elucidation.The IVF outcome and influencing factors of URPL patients need further study.Methods:A retrospective cohort study was designed,and 312 infertile patients with URPL who had been treated during January 2012 to December 2015 in the Reproduction Center of Peking University Third Hospital were included.By comparing clinical outcomes between these patients and those with tubal factor infertility(TFI),the factors affecting the clinical outcomes of URPL patients were analyzed.Results:The clinical pregnancy rate(35.18%vs.34.52%in fresh ET cycles,P=0.877;34.48%vs.40.27%in frozen-thawed ET cycles,P=0.283)and live birth rate(LBR)in fresh ET cycles(27.67%vs.26.59%,P=0.785)were not significantly different between URPL group and TFI group.URPL group had lower LBR in frozen-thawed ET cycles than that of TFI group(23.56%vs.33.56%,P=0.047),but the cumulative LBRs(34.69%vs.38.26%,P=0.368)were not significantly different between the two groups.The increased endometrial thickness(EMT)on the human chorionic gonadotropin day(odds ratio[OR]:0.848,95%confidence interval[CI]:0.748-0.962,P=0.010)and the increased number of eggs retrieved(OR:0.928,95%CI:0.887-0.970,P=0.001)were protective factors for clinical pregnancy in stimulated cycles.The increased number of eggs retrieved(OR:0.875,95%CI:0.846-0.906,P<0.001),the increased two-pronucleus rate(OR:0.151,95%CI:0.052-0.437,P<0.001),and increased EMT(OR:0.876,95%CI:0.770-0.997,P=0.045)in ET day were protective factors for the cumulative live birth outcome.Conclusion:After matching ages,no significant differences in clinical outcomes were found between the patients with URPL and the patients with TFI.A thicker endometrium and more retrieved oocytes increase the probability of pregnancy in fresh transfer cycles,but a better normal fertilization potential will increase the possibility of a live birth.

Genetic testing and PGD for unexplained recurrent fetal malformations with MAGEL2 gene mutation

Birth defects are caused by multiple factors,such as chromosome abnormality,environmental factors,and maternal factors.In this study,we focused on exploring the genetic causes of a non-consanguineous couple who suffered from four times of unsuccessful pregnancy due to unexplained recurrent fetal malformations with similar symptoms and normal chromosome copy number variations.Using trio-whole exome sequencing(trio-WES) for this couple and one of the affected fetuses,we found a mutation,c.1996 delC on the maternal imprinted gene MAGEL2 that was carried by the affected fetus and husband,leading to Schaaf-Yang syndrome.To screen this mutation,we further performed preimplantation genetic diagnosis(PGD) strategy followed by a gene pedigree validation and pathogenicity analysis.After the transfer of a PGD-screened embryo,a normal newborn without previous abnormal symptoms was born(February 15,2019).We present the first data that identified a pathogenic gene(MAGEL2 c.1996 delC) in a fetus with Schaaf-Yang syndrome in the EAS(East Asian) database and overcame this genetic defect by using processed PGD for this couple based on the WES results.