脱氢表雄酮(DHEA)在卵巢储备功能低下妇女中的应用进展

随着女性生育年龄的推迟,年龄相关的不孕症明显增加。如何改善卵巢低反应妇女的卵巢储备功能,提高对卵巢刺激的反应性,逐渐成为研究的热点。近年来,越来越多的生殖医学中心开始使用脱氢表雄酮(DHEA)对卵巢储备功能低下的患者进行治疗。研究表明使用DHEA后可增加获卵数,改善胚胎质量,提高妊娠率,减少流产率。尽管DHEA副作用小,但是由于其有效性还缺乏足够的循证医学证据的支持,因此目前还不能被推荐在临床上广泛使用。     

克罗米芬对卵巢储备功能减退患者进行促排卵治疗的有效性研究

目的:研究IVF/ISCI治疗中克罗米芬(CC)用于卵巢储备功能减退(DOR)患者促排卵治疗的效果。方法:回顾性分析年龄<35岁但基础FSH≥12 IU/L,或者年龄≥35岁患者的388个CC联合人绝经期促性腺素(hMG)的促排卵周期全胚行冻融胚胎移植(FET)的治疗结局,所有患者既往有≥1次促排卵治疗失败史。结果:年龄<35岁组,获卵数为4.5±3.1个,有效胚胎数为2.2±1.8个,优质胚胎数为1.6±1.5个,用药时间为8.8±2.0 d。在年龄≥35岁的患者中,获卵数为4.5±2.8个,有效胚胎数为2.2±1.8个,优质胚胎数为1.9±1.6个,用药时间为8.8±1.9 d。FET的临床妊娠率2个年龄组分别为37.8%和36.4%,组间无统计学差异(P>0.05)。结论:对于基础FSH水平高或者年龄≥35岁的DOR患者,CC联合hMG是一种有效的促排卵方案。     

Effect of Vasopressin Injection Technique in Laparoscopic Excision of Bilateral Ovarian Endometriomas on Ovarian Reserve: Prospective Randomized Study

Study ObjectiveTo evaluate the effects of vasopressin injection technique in laparoscopic cystectomy on ovarian reserve in patients with bilateral endometriomas.DesignRandomized prospective study (Canadian Task Force classification I).SettingUniversity hospital.PatientsEighty-six women with bilateral endometriomas.InterventionsLaparoscopic cystectomy of bilateral endometriomas was performed using different techniques including laparoscopic cystectomy by stripping without injection (control group), laparoscopic cystectomy by stripping with injection of saline solution (saline group), and laparoscopic cystectomy by stripping with vasopressin injection technique (VIT group).Measurements and Main ResultsThe number of coagulation events on the ovarian cortex for hemostasis was counted in different groups, and the thickness of ovarian tissues removed was measured. The basal follicle-stimulating hormone (FSH) level was determined before surgery and at 3-, 6-, and 12-month follow-up after laparoscopic cystectomy in the different groups. In the saline group, fewer coagulation events were required to achieve hemostasis, less ovarian tissues were removed, and lower preoperative FSH levels were detected than in the control group (p < .01). In the VIT group, even fewer coagulation events (p < .01) and lower preoperative FSH levels (p < .01) were detected than in the saline group. There was no significant difference in the thickness of ovarian tissues removed in the 2 groups (p > .05). Basal FSH levels were significantly different before and after surgery in the control and saline groups (p < .01) but not in the VIT group (p > .05).ConclusionVasopressin injection is an ideal procedure to reduce damage from usual laparoscopic cystectomy of bilateral ovarian endometriomas to protect ovarian reserve.     

Safety of Flibanserin in Women Treated With Antidepressants: A Randomized,Placebo-Controlled Study

Background

Depression is often associated with sexual dysfunction, and pharmacologic treatment for hypoactive sexual desire disorder can be considered in women receiving treatment for depression.

A Randomised,Double-Blinded,Placebo-Controlled Study of the Phosphodiesterase Type 5 Inhibitor Sildenafil for the Treatment of Preeclampsia

Objective:?To determine if the phosphodiesterase type 5 inhibitor sildenafil prolongs pregnancy in women with preeclampsia.?Methods:?Women with preeclampsia at gestational ages 24–34 weeks were recruited from nine hospitals in the UK, and randomly assigned to sildenafil citrate or placebo. Medication was increased every 3 days from 20 mg three times daily (tid), to 40 mg, and 80 mg tid. The primary endpoint was prolongation of pregnancy from randomisation to delivery (days). Secondary endpoints were markers of maternal disease and cord pH at delivery and infant weight. Details of all adverse events were also collected. Plasma samples were taken to establish pharmacokinetic information. Data analysed on a modified intention to treat analysis. The study had a power of >95% to detect a difference of 5 days.?Results:?Of 35 women, 17 were allocated to sildenafil and 18 to placebo. There was no difference in time from randomisation to delivery in the two treatment groups, with a median time of 4 days (range 1–15) in the sildenafil group and 4.5 days (range 1–30) in the placebo group. Sildenafil achieved maximum drug concentrations of 48 ng/ml, 88 ng/ml, and 271 ng/ml after 3 days of 20 mg, 40 mg and 80 mg tid, respectively.?Conclusion:?We have safely conducted a clinical trial of a drug not routinely used during pregnancy. Sildenafil in the escalating dose regimen 20–80 mg tid was well tolerated, with no increase in maternal or fetal morbidity or mortality but did not prolong pregnancy duration in women with preeclampsia. (ClinicalTrials.gov number, NCT 00141310).     

Postoperative Symptoms Following LLETZ or Radical Cervical Diathermy with Fulgaration: A Randomized Double-Blinded Prospective Study

Fifty-five patients were randomized in a double-blinded manner to large loop excision of the transformation zone (LLETZ) (29 patients) or radical cervical diathermy with fulgaration (RCDF) (26 patients) for treatment of cervical intraepithelial neoplasia (CIN). Patients completed a 2-month diary of symptoms and completed a 10-week postoperative questionnaire. White vaginal discharge lasted 7.3 (4.6) days (SD) for RCDF compared to 3.4 (1.6) days (SD) for LLETZ. There was no significant difference in any other symptoms on analysis This appears to be the first report clearly assessing the length and severity of postoperative symptoms following LLETZ or RCDF. There is no reason on length and severity of postoperative symptoms to choose 1 of these 2 treatment methods over the other.     

Optimal Dose of Pituitrin in Laparoscopic Uterine Myomectomy: A Double-Blinded,Randomized Controlled Trial

Study ObjectiveTo determine the optimal effective dose of pituitrin in laparoscopic myomectomy for uterine leiomyoma.DesignDouble-blinded, randomized controlled trial.SettingTertiary women's hospital in China.PatientsTotal of 118 patients who underwent laparoscopic myomectomy.InterventionsPatients randomly received 0, 2, 4, or 6 units of pituitrin injected into the myometrium surrounding the myoma.Measurements and Main ResultsRate of satisfactory surgical condition, hemodynamic changes, total surgical time, and blood loss were recorded. The rates of satisfactory surgical conditions were 6.7%, 72.4%, 89.7%, and 93.3% in groups 0U, 2U, 4U, and 6U, respectively; they were higher in groups 2U, 4U, and 6U than those in group 0U, but there were no significant differences among the groups 2U, 4U, and 6U. The blood loss was higher in group 0U than that in groups 2U, 4U, and 6U (p < .01). Pituitrin was associated with a transient decrease in blood pressures and an increase in heart rate in a dose-dependent fashion, with more pronounced changes in groups 4U and 6U, and these groups also required a higher amount of vasoactive drug to correct hemodynamic changes (p < .05).ConclusionTwo units of pituitrin could provide a satisfactory surgical field with minimal hemodynamic changes for laparoscopic uterine myomectomy.     

Impact of Ultrasound-Guided Transvaginal Ovarian Needle Drilling Versus Laparoscopic Ovarian Drilling on Ovarian Reserve and Pregnancy Rate in Polycystic Ovary Syndrome: A Randomized Clinical Trial

Study Objective

To compare the impact of ultrasound-guided transvaginal ovarian needle drilling (TND) versus laparoscopic ovarian drilling (LOD) on ovarian reserve and pregnancy rate in patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS).

Therapeutic Efficacy of Catheter-directed Ethanol Sclerotherapy and Its Impact on Ovarian Reserve in Patients with Ovarian Endometrioma at Risk of Decreased Ovarian Reserve: A Preliminary Study

Study ObjectiveTo investigate the therapeutic efficacy of catheter-directed ethanol sclerotherapy (CDS) and its effect on ovarian reserve in patients with endometrioma at risk of decreased ovarian reserve.DesignRetrospective study.SettingTeaching hospital.PatientsWe evaluated 18 patients with ovarian endometrioma measuring ≥3 cm and preprocedural serum antimüllerian hormone (AMH) levels of <2 ng/mL.InterventionsAn 8.5-F catheter was inserted either transabdominally or transvaginally into the endometrioma. After aspiration, sclerotherapy with 99% ethanol was performed, with a subsequent 20-minute ethanol retention.Measurements and Main ResultsUltrasonography was performed preprocedurally and 6 months after CDS to evaluate any recurrence or changes in cyst size. Furthermore, serum AMH levels, cancer antigen 125 (CA-125) levels, and the visual analog scale scores for dysmenorrhea were obtained to analyze the ovarian reserve and treatment efficacy, preprocedurally and at 6 months after CDS. The mean cyst size on ultrasonography and serum CA-125 levels decreased 6 months after CDS (p <.001 and p = .001, respectively). All patients reported a decreased visual analog scale score for dysmenorrhea (p <.001). However, the difference in serum AMH levels before and after CDS was statistically insignificant (p = .875).ConclusionCDS was efficacious in reducing pain and serum CA-125 levels in patients with low AMH levels without adversely affecting their ovarian reserve.     

Erythropoietin Treatment under Polychemotherapy in Patients with Gynecologic Malignancies: A Prospective, Randomized, Double-Blind Placebo-Controlled Multicenter Study

In order to examine the influence of erythropoietin (rHuEPO) on serum hemoglobin levels, transfusion requirements, and quality of life in patients with gynecologic malignancies under polychemotherapy and chronic tumor anemia (hemoglobin <11 g/dl), we performed a prospective, randomized, double-blinded placebo-controlled clinical trial. Between October 1992 and October 1993, 35 patients from 5 gynecologic departments were entered into this trial. Inclusion criteria were hemoglobin level <11 g/dl, ferritin level >29 ng/ml, stool negative for occult blood, and life expectancy for more than 3 months. Patients received either 150 U/kg body wt rHuEPO (Erypo by Cilag-Janssen) sc three times a week for 12 weeks (n= 23) or a placebo (n= 12). If the hemoglobin levels of the 4th, 8th, or 12th week were >2 g/dl above the baseline value and/or >12 g/dl, the patient was classified as a responder. Patients who required blood transfusions (hemoglobin <8 g/dl, erythrocytes <3 × 10⁶/ml, or clinical symptoms of anemia) were classified as nonresponders. A nonvalidated quality of life questionnaire was completed by the patient at the beginning of the treatment and then every fourth week before receiving chemotherapy. In the rHuEPO group 56.6% of the patients responded to the treatment (χ²= 10.79,P= 0.001) and only 5 patients (21.7%) required blood transfusions, whereas 8 of 12 patients in the placebo group (66.6%) had to be transfused (χ²= 6.81,P= 0.009). Quality of life did not differ significantly between the rHuEPO group and the placebo group of patients. Within the rHuEPO group those patients that responded showed a significant increase in physical activity after response in comparison to the preresponsive phase (P= 0.02, pairedttest). We therefore concluded that rHuEPO significantly increases serum hemoglobin levels and decreases transfusions requirements while maintaining quality of life in patients with gynecological malignancies who are undergoing polychemotherapy.     

四种预测卵巢储备指标的临床研究

目的 :在体外受精 胚胎移植 (IVF ET)患者中对预测卵巢储备的 4种指标进行临床研究 ,以期寻找 1～ 2种灵敏度高的指标用于普通不孕人群。方法 :随机选择不同年龄段的 90例不孕患者 ,在接受IVF ET前 1～ 2个周期 ,于月经第 3天取空腹血测定基础性激素水平 ;于月经第 5～ 9天服氯米酚 (CC) 10 0mg,第 10天取空腹血测定FSH、LH、E2 ;开始进入IVF ET周期前 ,B超测量卵巢体积 ,观察IVF ET过程中卵巢的反应性。结果 :随年龄增加 ,卵巢反应不良及取消周期的比例增加 ;随基础FSH、服CC后FSH水平升高 ,卵巢反应性降低。卵巢体积较小组 ,卵巢反应不良的比例占 5 2 0 %。结论 :年龄是一个较为敏感的指标 ;基础FSH水平对卵巢储备的评估优于CC兴奋试验和卵巢体积测定。由于B超检查简便无侵入性 ,因此 ,认为基础FSH水平配合年龄和卵巢体积综合评估 ,将有助于提高预测价值。     

Effect of l-Arginine Supplementation on Blood Pressure in Pregnant Women: A Meta-Analysis of Placebo-Controlled Trials

Objective. A meta-analysis of placebo-controlled trials was conducted to evaluate the effect of l-arginine supplementation on blood pressure (BP) in pregnancy. Methods. Trials were searched in PubMed, Embase, and Cochrane Library. A total of five trials were included in the meta-analysis. Results. l-Arginine supplementation exhibited a mean decrease of 3.07 mmHg (p = 0.004) for diastolic blood pressure and a mean increase of 1.23 weeks (p = 0.002) for gestation age at delivery in pregnancy, but did not reduce systolic BP (p = 0.19) as compared to placebo. Conclusion. l-Arginine supplementation had a significant effect of lowering diastolic blood pressure and prolonging gestation age in pregnancy.     

卵巢储备功能测定在体外受精(IVF)技术中的临床价值探讨

目的:探讨在体外受精-胚胎移植技术中对超促排卵最具临床价值的卵巢储备功能测定指标。方法:将2003.10-2004.10间,105例接受IVF-ET治疗的不孕患者的年龄、基础FSH值、基础窦卵泡数、卵巢体积和卵巢基质血流测定指标与IVF超排中卵巢的实际反应进行对比并作相关性分析。结果:年龄、FSH与获卵数呈非常显著负相关,与促性腺激素(Gn)注射支数呈显著正相关;窦卵泡数、卵巢体积与获卵数呈非常显著正相关,与Gn注射支数呈非常显著负相关;其中以基础窦卵泡数与卵巢反应关系最为密切。卵巢基质血流与卵巢反应无显著相关。结论:年龄、基础FSH值、阴道超声测量基础窦卵泡数和卵巢体积均能预测超排时卵巢对促性腺激素刺激的反应性,并有简便、经济之优点,其中以窦卵泡计数的预测价值最高,窦卵泡计数不仅可用于卵巢低反应的预测,还可预测卵巢反应过激,而年龄与基础FSH仅在预测卵巢低反应中较为敏感,卵巢基质血流对预测卵巢反应的意义有待进一步探讨。     

Extracorporeal Shock Wave Therapy in Peyronie's Disease: Results of a Placebo-Controlled,Prospective, Randomized,Single-Blind Study

IntroductionExtracorporeal shock wave therapy (ESWT) for treatment of Peyronie's disease (PD) is controversial.AimTo study the efficacy of ESWT by a placebo-controlled, randomized trial.MethodsPatients with PD (n = 102) were randomly assigned (n = 51) to each group (ESWT or placebo). All patients were given 6 weekly treatments. Patients in the ESWT-group received 2,000 shock waves per session, using the Piezoson 100 lithotripter (Richard Wolf, Knittlingen, Germany). Patients in the placebo-group were treated with interposition of a plastic membrane, which prevented any transmission of shock waves.Main Outcome MeasuresPrimary end point was decrease of pain between baseline and after 4 weeks follow-up. Secondary end points were changes in deviation, plaque size, and sexual function. Pain was assessed by a visual analog scale. Deviation was measured by a goniometer after artificial erection using Alprostadil (Viridal^®, Schwarz Pharma, Monheim, Germany). Plaque size was measured with a ruler and sexual function assessed by a scale regarding the ability to perform sexual intercourse.ResultsOverall, only 45 patients experienced pain at baseline. In the subgroup analysis of these patients, pain decreased in 17/20 (85.0%) patients in the ESWT group and 12/25 (48.0%) patients in the placebo group (P = 0.013, relative risk [RR] = 0.29, 95% confidence interval: 0.09–0.87). Penile deviation was not reduced by ESWT (P = 0.66) but worsened in 20/50 (40%) and 12/49 (24.5%) patients of the ESWT and placebo-group, respectively (P = 0.133). Plaque size reduction was not different between the two groups (P = 0.33). Additional, plaque size increased in five patients (10.9%) of the ESWT group only. An improvement in sexual function could not be verified (P = 0.126, RR = 0.46).ConclusionsDespite some potential benefit of ESWT in regard to pain reduction, it should be emphasized that pain usually resolves spontaneously with time. Given this and the fact that deviation may worsen with ESWT, this treatment cannot be recommended. Hatzichristodoulou G, Meisner C, Gschwend JE, Stenzl A, and Lahme S. Extracorporeal shock wave therapy in Peyronie's disease: Results of a placebo-controlled, prospective, randomized, single-blind study. J Sex Med 2013;10:2815–2821.     

Endometrioma Excision and Ovarian Reserve: A Dangerous Relation

Endometrioma is one of the most frequent pathologies in gynecologic surgery. Laparoscopic cyst excision is considered the best treatment in terms of lower recurrence and improved fertility. However, it was recently questioned whether the excision of the endometrioma could decrease the function of the operated ovary and if it could affect the subsequent fertility. Even if a consistent amount of ovarian tissue is unintentionally removed together with the capsule of the cyst, resulting in does not show the follicular pattern observed in working ovaries. Currently, no definitive data clarify whether the damage to the ovarian reserve, observed in patient with endometrioma, is related to the surgical procedure, to the previous presence of the cyst, or both. Electrosurgial coagulation during hemostasis could play an important role in terms of damage to ovarian stroma and vascularization. Particular attention must be paid in presence of bilateral endometriotic cysts. In fact, an increase in premature ovarian failure rate was reported when both the ovaries are involved in surgery. Incase of assisted reproductive techniques, no clear evidence indicates which is the best approach for concomitant endometriotic cyst. On the base of these considerations endometriomas Should be treated only in case of pain, infertility, and in asymptomatic patients if the cyst diameter is greater than 4 cm.     

Daily Oral l-Arginine Plus Tadalafil in Diabetic Patients with Erectile Dysfunction: A Double-Blinded,Randomized, Controlled Clinical Trial

IntroductionErectile dysfunction is a common condition among diabetic men. Many treatments are now available with variable responses.AimThis study aimed to evaluate the effect of daily oral l-arginine plus tadalafil in diabetic patients with mild to moderate erectile dysfunction.MethodsA double-blinded, randomized, controlled clinical trial was conducted with 108 diabetic male patients. Each patient was assessed by medical and sexual histories, International Index of Erectile Function 5-item questionnaires, pharmaco-penile duplex ultrasonography, and serum testosterone level.Main Outcome MeasureImprovement in International Index of Erectile Function 5-item, serum testosterone level and pharmaco-penile duplex ultrasonography.ResultsErectile functions were significantly improved in all patients after treatment as compared with baseline and placebo (P < .001). Patients who received both drugs showed significant improvement compared to those treated with single drugs, as assessed by International Index of Erectile Function scores and total testosterone (P < .001). Pharmaco-penile ultrasound duplex results showed non-significant differences among patients treated with both drugs and those with each drug alone.ConclusionDaily use of l-arginine with tadalafil significantly increased the International Index of Erectile Function scores and total testosterone levels as compared to each drug alone in diabetic patients with erectile dysfunction. No differences were found based on pharmaco-penile duplex findings.El Taieb M, Hegazy E, Ibrahim A. Daily Oral l-Arginine Plus Tadalafil in Diabetic Patients with Erectile Dysfunction: A Double-Blinded, Randomized, Controlled Clinical Trial. J Sex Med 2019; 19:1390–1397.     

Platelet-Rich Plasma (PRP) Improves Erectile Function: A Double-Blind,Randomized, Placebo-Controlled Clinical Trial

BackgroundAnimal studies postulate that platelet-rich plasma (PRP) injections improve key elements of the pathophysiologic mechanisms leading to erectile dysfunction (ED).AimTo conduct the first double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of PRP injections in patients with mild and moderate ED.MethodsSixty sexually active patients with mild and moderate ED were randomly assigned to two sessions, with a one-month difference, of 10 mL PRP (n = 30) or placebo (n = 30) intracavernosal injections. An FDA-approved separation system was used. Patients were evaluated at 1, 3 and 6 months after completion of the treatment protocol. A per-protocol analysis was applied. All participants withheld any ED treatment during the trial.OutcomesThe achievement of minimal clinically important difference (MCID) in the International Index of Erectile Function – Erectile Domain (IIEF-EF) from baseline to 6 months after final treatment. Erectile function at all time points, as well as safety of PRP injections, were also evaluated.ResultsAt 6 months, a MCID was achieved by 20/29 (69%) patients in the PRP group compared to 7/26 (27%) in the placebo group. The risk difference between the two groups was 42% (95%CI: 18?66), P < 0.001 and the baseline-adjusted mean between-group-difference in the IIEF-EF score was 3.9 points (95%CI: 1.8?5.9). Similarly, a statistically significant difference of both the number of participants attaining a MCID and the IIEF-EF score was also observed at the 1- and 3-month evaluation between the two groups. Accordingly, patients receiving PRP were more satisfied with the treatment. No adverse events were observed during the study period.Clinical implicationsIntracavernosal PRP injection therapy used as outlined in this trial appears to be a safe and effective short-term treatment for the management of mild to moderate ED.Strengths & LimitationsWe conducted the first clinical trial exploring the role of PRP in the management of ED. Conversely, our findings lack external validity due to single-center design. Furthermore, our results cannot be extrapolated to other PRP separation systems.ConclusionsPRP intracavernosal injections may be a promising addition to the urologist's armamentarium for the management of ED. Still, further high-quality studies are warranted to corroborate our findings. Evangelos P, Mykoniatis I, Pyrgidis N, et al. Platelet-Rich Plasma (PRP) Improves Erectile Function: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Sex Med 2021;18:926–935.     

Intrauterine Instillation of Tranexamic Acid in Hysteroscopic Myomectomy: A Double-Blind,Placebo-Controlled,Parallel-Group Randomized Clinical Trial

Study ObjectiveTo evaluate the hemostatic effect of intrauterine instillation of tranexamic acid (TXA) with the distention medium during hysteroscopic myomectomy.DesignProspective, parallel-group, double-blind, placebo-controlled randomized clinical trial.SettingEarly Cancer Detection Unit in Ain Shams University Maternity Hospital, Cairo, Egypt.PatientsEighty women with type 0 or I submucous myoma undergoing hysteroscopic myomectomy using unipolar resectoscope.InterventionsThe participants were randomly assigned to receive either 1 g of TXA for every 1000 mL of the distending medium (intervention group) or 10 mL of placebo (10 mL of 1.5% glycine) in the same form inside every 1000 mL of the distention medium.Measurements and Main ResultsThe primary outcome was a change in hemoglobin level 24 hours after surgery compared with preoperative values, and the secondary outcomes were the surgeon's rating of intraoperative bleeding and the quality of operative view, the duration of surgery, the volume of injected media, intraoperative complications, and the completion of myomectomy in 1 procedure. The mean difference in hemoglobin level was 1.11 ±.58 g/dL in the TXA group and 1.46 ± 0.61 g/dL in the placebo group (p = .015). The quality of hysteroscopic view was better in the TXA group (p = .001), with good operative view in 23 (60.5%) cases in TXA vs 8 (20.5%) in the placebo group. The surgeon's rating of bleeding as excessive was reported in 1 (2.6%) case in the TXA group and in 9 (23.1%) cases in the placebo group. There was no difference between the groups regarding the duration of surgery, the volume of injected media, completion of myoma resection in 1 session, and intraoperative complications. Three cases of uterine perforation with the thermal loop were reported, and all were associated with poor operative field in the placebo group.ConclusionIntrauterine instillation of TXA with the distention medium during hysteroscopic myomectomy resulted in a statistically significant decrease in hemoglobin level 24 hours after surgery, albeit with minimal clinical significance. TXA resulted in better visualization of the field throughout the procedure.