Spontaneous ovarian hyperstimulation syndrome and pituitary hyperplasia mimicking macroadenoma associated with primary hypothyroidism

We report an unusual case of spontaneous ovarian hyperstimulation syndrome and pituitary hyperplasia mimicking macroadenoma in an adult,non-pregnant woman.Her condition was triggered by unrecognized primary hypothyroidism,which regressed after thyroid hormone replacement therapy.This case highlights the need for clinicians and radiologists to familiarize themselves with the clinical and imaging features detected in case of these complications of primary hypothyroidism,which are not well known in the medical and radiological profession.Such improved knowledge will help avoid delays in diagnosis,progression to lifethreatening complications,and unnecessary surgery.

Correlation of IL-1, IL-6, IL-10 Concentrations to Ovarian Hyperstimulation Syndrome and Effect of Intravenous Immunoglobulin on Ovarian Hyperstimulated Rats

Objective To investigate the correlation of interleukin（IL）-1,IL-6 and IL-10 concentrations to ovarian hyperstimulation syndrome（OHSS） and whether intravenous immunoglobulin（IVIG） has the effects on ovarian hyperstimulated rats. Methods Immature female Wistar rats were divided into control group, OHSS group （n=13） and IVIG group（n=13）. For the latter two groups, pregnancy mare serum gonadotropin（PMSG）and human chorionic gonadotropin（hCG） were given to induce OHSS, and rats in IVIG group were treated with immunoglobulin. Forty-eight hours after administration of hCG, capillary permeability was evaluated from the Evans blue dye（EB） concentration in the ovaries and the EB concentration in peritoneal irrigated fluid at 30 min after the intravenous injection of EB. Rats＇ blood samples and ovaries were obtained to be measured for IL-1, IL-6 and IL-10 by ELISA. Results In OHSS group, total weights of bilateral ovaries and the ovarian EB concentration were significantly higher than those in others（P〈0.05）. Both serum and ovarian concentrations of IL-1 were significantly higher in OHSS and IVIG groups than those in control group （P〈0.05）. The ovarian concentrations of IL-6 and IL-10 in IVIG group were significantly lower than those in control group（P〈0.05）. Furthermore, the ovarian IL-10 concentration in IVIG group was significantly lower than that in OHSS group（P〈0. 05）. Conclusion Inflammation involved IL-1 in OHSS rats plays an important role. Vascular permeability was mostly increased in ovaries of hyperstimulated rats. It appears that ovaries of OHSS rats may be the primary places of inflammation. IVIG treatment resulted in statistically significant reductions in ovaries＇ weights and ovarian vascular permeability of OHSS rats, with a decreased level of ovarian IL-10. It implys that IVIG have a beneficial effect in reducing the severity of OHSS in the experimental model maybe by restrainning IL-10.

A Second Dose of GnRHa in Combination with Luteal GnRH Antagonist May Eliminate Ovarian Hyperstimulation Syndrome in Women with≥30 Follicles Measuring≥11 mm in Diameter on Trigger Day and/or Pre-trigger Peak Estradiol Exceeding 10 000 pg/mL

This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome(OHSS),characterized by more than 30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.which was also the feature of women with established severe early OHSS followed by gonadotrophin-releasing hormone agonist(GnRHa)trigger and freeze-all policy that previously have been reported.All patients received a second dose of GnRHa 12 h after the first GnRHa trigger combined with administration of GnRH antagonist at 0.25 mg/day for a period of 3 days from the day of oocyte retrieval onwards.The in vitro fertilization(IVF)outcomes may be preferable compared with a bolus of GnRHa trigger and none of the included patients developed moderate-to-severe OHSS.Moreover,patients'symptoms,reproductive honnone levels and ultrasound findings were improved significantly.This new strategy seems to be efficacious and could be a further supplement of GnRHa trigger with or without applying freeze-all strategy to completely prevent early-onset moderate to severe OHSS,especially for the patients characterized by≥30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.Further studies should be performed to compare this regimen with conventional methods of OHSS prevention.

The Influence of Cabergoline and Coasting in Prevention of the Ovarian Hyperstimulation Syndrome in Patients Undergoing IVF/ICSI-ET Treatment: A Systematic Review and Meta-Analysis

Objective: To compare the effectiveness of two methods in preventing ovarian hyperstimulation syndrome (OHSS) with cabergoline and coasting. Design: Systematic review and meta-analysis of randomized clinical trials (RCTs). Patients: Women were considered as have risk of OHSS undergoing fertility treatment. Interventions: Cabergoline, coasting. Result: There were included five RCT studies. The clinical pregnancy rate was no significantly difference between two groups (RR 1.22, 95% CI [0.86, 1.71]), implantation rate (RR 1.00, 95% CI [0.75, 1.32]), severe OHSS (RR 0.93, 95% CI [0.38, 2.31]), fertilization rate (SMD 0.70, 95% CI [-0.10, 1.50]), number of oocytes retrieved (SMD 0.80, 95% CI [0.30, 1.30]), number of embryo transfer (SMD-0.04, 95% CI [-0.24, 0.17]), E2 value on the day of HCG injection (SMD 0.21, 95% CI [-0.25, 0.68]), number of MII oocytes (SMD 0.71, 95% CI [0.32, 1.11]), abortion rate (RR 0.61, 95% CI [0.21, 1.83]), number of follicles > 17 mm on day of HCG (SMD -0.01, 95% CI [-0.26, 0.24]), number of follicles 15 - 17 mm on day of HCG (SMD -0.08, 95% CI [-0.33, 0.17]), number of follicles 10 - 14 mm on day of HCG (SMD -0.06, 95% CI [-0.31, 0.19]). Conclusion: Both cabergoline and coasting prevent the occurrence of OHSS, but no statistically significant difference between them. Compared with coasting group, a daily dose of 0.5 mg cabergoline significantly increased the number of oocytes retrieved, MII oocytes, and fertilization rate, but decreased the abortion rate.

Spontaneous ovarian hyperstimulation syndrome: Report of two cases

BACKGROUND Spontaneous ovarian hyperstimulation syndrome(s OHSS) is extremely rare. It can be divided into four types according to its clinical manifestations and follicle stimulating hormone receptor mutations.CASE SUMMARY Here we report two cases of s OHSS in Chinese women, one with a singleton gestation developing s OHSS in the first trimester who conceived naturally and the other with a twin pregnancy developing s OHSS in the second trimester after a thawed embryo transfer cycle. Both patients were admitted to the hospital with abdominal distension, ascites, and enlarged ovaries. Conservative treatment was the primary option of management. The first patient had spontaneous onset labor at 40 wk of gestation and underwent an uncomplicated vaginal delivery of a male newborn. The second patient delivered a female baby and a male baby by caesarean section at 35 wk and 1 d of gestation.CONCLUSION Patients with a history of ovarian hyperstimulation syndrome should be closely monitored. Single embryo transfer might reduce the risk of this rare syndrome.

Common carotid artery thrombosis and malignant middle cerebral artery infarction following ovarian hyperstimulation syndrome:A case report

BACKGROUND Arterial thrombosis is a serious and rare complication of ovarian hyperstimulation syndrome(OHSS).Herein,we describe a case of OHSS complicated by common carotid artery thrombosis and malignant middle cerebral artery infarction after egg retrieval and before embryo transfer.CASE SUMMARY A 32-year-old female with a family history of thrombosis who was undergoing in vitro fertilization due to unexplained infertility,was admitted due to abdominal distension for 3 d and coma for 2 h.She received egg retrieval 7 d ago and embryo transfer had not yet been performed.Blood biochemical analysis showed estrogen of 15781 pmol/L.Gynecological examination showed palpable masses on both sides of the adnexal areas.Ultrasound observed enlarged ovaries and abdominal ascites.Imaging examination of the head and neck revealed fresh malignant middle cerebral artery infarction in the left side of brain and internal carotid artery as well as occlusion in the left carotid artery,internal carotid artery,and middle cerebral artery.The patient was finally diagnosed with severe OHSS,complicated by common carotid artery thrombosis and malignant middle cerebral artery infarction.Liquid replacement,anticoagulation,vascular endothelium protection,brain protection and decompressive craniectomy were carried out.Rehabilitation training was then performed for 6 mo.At present,she has poor speaking ability and decreased muscle strength on the right side.CONCLUSION There is a risk of thrombosis during any period of OHSS.During in vitro assisted reproduction,for cases with a family history of thrombosis,hyperlipidemia and other high-risk factors,serum lipid levels should be controlled as soon as possible to improve metabolic dysfunction.When thrombosis occurs,timely and effective treatment should be performed to improve the prognosis.

Clinical analyses for 93 cycles of moderate and severe ovarian hyperstimulation syndrome

Objective:To investigate the high risk factors and methods of prevention and treatment of ovarian hyperstimulation syndrome (OHSS) in assisted reproductive techniques (ART).Methods: Clinical data of 93 cycles of OHSS patients after IVF-ET treatment from Apr. 1989to Oct. 2002 were analyzed retrospectively.Results: (1) A large number of follicles stimulated, luteal phase support with HCG and pregnancy were high risk factors to induce OHSS. (2) Longer disease process, more severe symptoms and more albumins used for treatment of OHSS were commonoy observed in pregnant patients with OHSS compared with non-pregnant ones. (3) Vena dropping human serum albumin is one of the most successful treatment as plasma expanders through restoration of colloid osmotic pressure; paracentesis is necessary for critical OHSS patients with severe ascites and hydrothorax;(4) Occasionally therapeutic abortion of an early gestation may be an only way for lifesaving when all other methods have failed.Conclusions: OHSS is a serious complication of controlled ovarian hyperstimulation. Proper prevention and treatment of OHSS are important for patient safety in ART.

Follicular Aspiration Is Superior to Coasting as Effective Prophylactic Procedure against Ovarian Hyperstimulation Syndrome

Objectives: Evaluation of outcome follicular aspiration compared to coating procedure for infertile women undergoing ICSI regarding frequency and severity of ovarian hyperstimulation syndrome (OHSS). Patients & Methods: Infertile PCOS women underwent controlled ovarian stimulation with luteal phase GnRH-agonist long down-regulation protocol. Women developed serum E2 level > 4000 pg/ml and/or >20 follicles of ≥10 mm in diameter were randomly divided to receive coasting strategy (Coasting group) or TVU-guided aspiration (Aspiration group). When ≥3 follicles were ≥18 mm and serum E2 level was and 10,000 IU was administered 36 h before oocyte retrieval, and ICSI was performed 72-hr thereafter and the frequency of moderate-to-severe OHSS was determined. Results: 82 women developed criteria for categorization and 21 women (25.6%) developed moderate-to-severe OHSS;5 women of aspiration and 16 of Coasting group;with significantly (P = 0.005) lower frequency in aspiration group. Twenty women developed ascites;3 women had clinically detectable, while 17 women had US detected ascites with significantly (P = 0.039) higher frequency among women that had coasting. All other manifestations of OHSS were significantly lower with aspiration procedure. Both coasting and aspiration therapy significantly reduced serum E2 and ovarian diameter on day of hCG injection compared to estimates taken at time of categorization. Conclusion: Coasting procedure prior to hCG injection could decrease incidence of OHSS and lessens its manifestation. Follicular aspiration provided more superior results and improved outcome of these women. Any of these modalities could be provided to infertile high-risk women according to the availability of experiences and patients’ selection.

Ovarian hyperstimulation syndrome following the use of GnRH agonist trigger of final oocyte maturation and freeze-all strategy: A case report and review of the literature

Rationale:The current literature has a surprising controversy regarding the use of low-dose human chorionic gonadotropin(hCG)for luteal support as an explanation for the development of ovarian hyperstimulation syndrome,and this is because of the gap in the listing of the predisposing factors that put women at an increased risk of ovarian hyperstimulation syndrome.Patient concerns:A case of 25-year-old woman presented with abdominal pain,distention,dyspnea,and nausea with a 6.5 kg increase in weight from baseline.Ultrasonographic examination showed bilaterally enlarged multicystic ovaries after gonadotropin-releasing hormone(GnRH)agonist triggering and cycle segmentation with no hCG rescue administration.Diagnosis:Moderate/severe ovarian hyperstimulation syndrome.Interventions:The woman was admitted to the hospital for medical management of moderate/severe ovarian hyperstimulation syndrome,and pain management was advanced to patient-controlled anesthesia with the start of low molecular weight heparin.On day 2,albumin therapy followed by a furosemide chase was started due to an increase in abdominal girth.On day 1,Cabergoline was maintained,and on day 2 the GnRH antagonist Cetrorelix was started.Outcomes:The woman’s clinical condition improved,and a clinical pregnancy was eventually achieved during the first cryo-warmed blastocyst cycle.Lessons:Ovarian hyperstimulation syndrome can still happen even after the use of GnRH agonist and avoidance of hCG support.Segmentation of in vitro fertilization with complete avoidance of hCG for luteal support remains the best approach.

Flexible GnRH Antagonist Protocol versus Progestin-primed Ovarian Stimulation (PPOS) Protocol in Patients with Polycystic Ovary Syndrome: Comparison of Clinical Outcomes and Ovarian Response

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.

The application of in vitro maturation of oocytes in the infertile patients with polycystic ovarian syndrome

Objective:To evaluate the effects of in vitro maturation(IVM)of oocytes in the infertile pa-tients with polyeystic ovarian syndrome(PCOS).Methods:The infertile patients with PCOS who underwent IVM or IVF/ICSI from January2004 to August 2005 were studied retrospectively.68 unstimulated cycles(48 cases)underwentIVM as IVM group,42 cycles(39 cases)underwent IVF/ICSI as control group.Main outcomesincluding the number of oocytes retrival,the rates of fertilization,embryo cleavage,implanta-tion,pregnancy,miscarriage,ovarian hyperstimulation syndrome(OHSS)and multiple pregnan-cy were assessed.Results:No FSH was administered in IVM group and the mean number of FSH used was(25±6.2)ampoules in control group.When compared with control group,women in IVM grouphad significant increase in fertilization rate(70.7% versus 63.9%)and decrease in cleavage rate(87.9% versus 99.4%)and ovarian hyperstimulation syndrome(0 versus 7.1%).No significantdifferences between IVM group and control group were found in the number of oocytes obtained,implantation rate,clinical pregnancy rate,miscarriage rate and multiple pregnancy rate.Conclusion:Our results suggested that for infertile PCOS women who required assisted con-ception treatment,IVM is a more economical method with less OHSS complication than that ofconventional IVF treatment.

Peripheral blood transcriptome analysis of patients with ovarian hyperstimulation syndrome through high-throughput sequencing

Objective:Ovarian hyperstimulation syndrome(OHSS)is a frequent iatrogenic complication that arises during assisted reproduction and accounts for approximately 30%of all in vitro fertilization cycles.Using high-throughput sequencing,we investigated the peripheral blood transcriptome of patients with OHSS.Methods:Peripheral blood samples were obtained from 15 patients in each of the OHSS high-risk and low-risk groups on the ovum pick-up day.Subsequently,high-throughput sequencing was used to obtain the peripheral blood transcriptomes of five patients each from the high-and low-risk groups.Bioinformatic tools were used for mRNA expression profile mapping and screening of differentially expressed genes(DEGs).Bioinformatics techniques were also implemented in the Kyoto Encyclopedia of Genes Genomes(KEGG)signal pathway,Gene Ontology(GO)function,and protein-protein interaction(PPI)network analyses of DEGs.Results:A total of 20,031 genes were identified and 148 were found to be differentially expressed(P<0.05,|log_(2)FC|>0.58),with 52 upregulated and 96 downregulated genes.GO and KEGG analyses indicated that these genes were involved in extracellular corpuscles(GO:0070062),plasma membrane(GO:0005886),extracellular regions(GO:0005576),immune system response(GO:0006955),PI3K-Akt signaling pathways(hsa04151),cell adhesion molecules(CAMs,hsa04514),focal adhesion(hsa04510),and complement and coagulation cascades(hsa04610).The PPI network and realtime fluorescence quantitative polymerase chain reaction(qPCR)verification predicted that complement C3,von Willebrand factor,and vascular cell adhesion protein 1 proteins are highly implicated in OHSS and may serve as potential biomarkers for future OHSS studies.Conclusion:Transcriptome analysis revealed several DEGs related to OHSS risk factors in the peripheral blood,indicating that these DEGs may be novel players in OHSS development.

Application of human growth hormone to patients with polycystic ovary syndrome during in vitro fertilization

Objective:To observe the effect of applying human growth hormone during in vitro fertilization to patients with polycystic ovary syndrome(PCOS) Methods:One hundred and twenty-one cycles of in vitro fertilization and embryo transfer in PCOS patients with anovulation from Dec.2008 to Nov.2010 were studied retrospectively.Of these 121 cycles,48 were with treatment of growth hormone(GH group),73 without GH treatment(control group).The dose of gonadotropin(Gn),the number of retrieved oocytes,good-quality embryo rate,implantation rate,frozen embryo rate,and pregnancy rate were compared. Results:The dosage of Gn was slightly higher in GH group than that in control group(29.18±8.33 vs.23.43±8.68 ampoullas,4U/ampoulla) and the number of retrieved oocytes in GH group were slightly less than that in control group(10.73±6.0 vs.14.0±8.57),but there were no significant differences(P>0.05).The good-quality embryo rate(59.1%vs.33.3%),frozen embryo rate(87.5%vs.58.9%),pregnancy rate(56.5%vs. 35.3%) and implantation rate(35.3%vs.20.4%) in GH group were all significantly higher than those in control group(P<0.05). Conclusion:Early usage of GH in the ovarian hyperstimulation in PCOS patients could significantly improve good-quality embryo rate,implantation rate and pregnancy rate.

Acceleration of coasting enhances pregnancy rate in ICSI cycles at risk for ovarian hyperstimulation syndrome

Objective To assess the efficacy of adding Gn-releasing hormone antagonist（GnR HA） on the day of hC G triggering in a long luteal protocol without withholding the agonist in women who are at a risk to develop ovarian hyperstimulation syndrome（OHSS）.Methods This was a retrospective cohort study conducted upon 50 women who have elevated serum estradiol（E2） level 〉4 500 ng/L at the day of ovum triggering with hC G on a long agonist luteal protocol of controlled ovarian stimulation（COS）. When an exaggerated ovarian response was observed around day 10 of stimulation, immediately the next morning at 6 a.m. gonadotropin administration was stopped or reduced, and a single dose of ganirelix acetate（antagonist） was given sc continuation of the agonist dose hC G. Another serum E2 measurement was done at 6 p.m.（after 12 h of antagonist） then hC G, sc 250 mg and choriogonadotropin α were administered 14 h later after antagonist and documented the reduction of E2 level. Oocyte retrieval was conducted after 34-36 h of hC G administration. The measured outcomes were the level of E2 on the day of hC G injection, number of oocytes and their quality, pregnancy rate and the occurrence of OHSS and its grade in case it happened.Results The total dose for recombinant FSH was 25.3±6.4 ampoules（75 IU/ampoule） while it was 11.0±3.0 ampoules for the urinary hM G. A higher oocyte maturation rate（82.8%） and a high fertilization rate（87.8%） were observed. The mean endometrial thickness was 10.1±1.0 mm on the day of hC G triggering. The higher fertilization rate with the good endometrial thickness observed resulting in a higher pregnancy rate（78.0%, 39/50） with statistically significant（P〈0.05）. A significant reduction of E2 level was documented by a percentage around 40% before hC Ginjection. There were no reported cases of severe or moderate OHSS, however 13 cases（26%） were reported to have mild OHSS constituting.Conclusion Acceleration of coasting in cases of OHSS through treatment with GnR HA after pituitary suppression with GnR H agonist（GnR H-a） offered a novel approach to decrease E2 level, avoided cycle cancellation, and maintain excellent oocyte maturation rate, and finally result in high pregnancy rate with prevention of OHSS.

个性化康复联合GnRH拮抗剂方案在OHSS高风险患者中的应用

目的探讨个性化康复联合促性腺激素释放激素拮抗剂(GnRH-A)方案在卵巢过度刺激综合征(OHSS)高风险助孕患者中的应用效果。方法选择86例OHSS高风险助孕患者,随机分为个性化康复组和对照组,每组各43例。2组患者均接受GnRH-A方案促排卵,在此基础上对照组接受常规康复方案,个性化康复组接受个性化康复方案。比较2组患者干预后OHSS总发生率,OHSS患者的住院时间、不适症状消退时间,患者焦虑和抑郁状态以及康复满意度。结果干预后与对照组相比,个性化康复组的OHSS总发生率、OHSS患者住院时间和不适症状消退时间,汉密尔顿抑郁评分和焦虑自评量表评分均低于对照组(P均<0.05)。干预后,个性化康复组的康复满意度高于对照组(P<0.05)。结论个性化康复联合GnRH-A方案可有效预防OHSS,缩短OHSS患者住院时间及不适症状持续时长,改善患者精神心理状态,提高康复满意度。

西曲瑞克联合阿司匹林预防早发型卵巢过度刺激综合征的疗效观察

目的观察西曲瑞克联合阿司匹林预防早发型卵巢过度刺激综合征(OHSS)的疗效。方法回顾性收集2022年1月1日至7月1日于我院治疗的38例早发型OHSS患者资料,根据用药方案的不同分为对照组(19例)和干预组(19例)。取卵术后第1天,对照组患者给予阿司匹林肠溶片100 mg,口服至月经来潮;干预组患者给予注射用西曲瑞克0.25 mg,连续3 d皮下注射+阿司匹林肠溶片(用法用量同对照组)。观察并检测两组患者的首个黄体期、OHSS严重程度分级及取卵术后卵巢体积、腹水体积、血清雌二醇(E_(2))、白细胞计数(WBC)、红细胞比容(HCT)、中性粒细胞百分比(NEUT%)、D-二聚体(DD)、凝血酶原时间(PT)、纤维蛋白原(Fib)。结果干预组患者的首个黄体期显著短于对照组,中、重度患者比例显著低于对照组(P<0.05或P<0.01)。取卵术后,干预组患者的卵巢体积、腹水体积、血清E_(2)、WBC、NEUT%、HCT、DD、Fib总体低于对照组,PT显著高于对照组(P<0.05)。结论西曲瑞克联合阿司匹林预防早发型OHSS的疗效较单用阿司匹林更好。

黄体期长方案与拮抗剂方案在首次拮抗剂失败后PCOS患者中的应用比较

目的探讨首次拮抗剂治疗失败的多囊卵巢综合征(PCOS)患者再次超促排卵时分别采用黄体期长方案和拮抗剂方案诱导排卵的临床效果及妊娠结局的优劣。方法检索首次采用拮抗剂方案行IVF/ICSI-ET助孕失败后再次超促排卵的PCOS患者163例,根据第二次超促排卵方案,分为黄体期长方案组(共95例)和拮抗剂方案组(共68例)。回顾性分析比较两组患者的基础临床资料、临床及实验室指标及妊娠结局。结果①两组患者的基础临床指标除了LH,其他指标差异均无统计学意义。②黄体期长方案组患者自身超排卵对比,促性腺激素(Gn)启动剂量、Gn总天数、Gn总使用量、hCG注射日雌二醇(E_(2))值、获卵数、卵子成熟率、2PN受精数、2PN卵裂数、囊胚形成率、优质囊胚形成率显著高于首次拮抗剂周期(P<0.05)。拮抗剂方案组患者自身超排卵对比也观察到类似改善。③两组第二次超促排卵周期比较,黄体期长方案组Gn总天数、总用量、总费用较高(P<0.05),而hCG注射日E_(2)及LH水平、卵子成熟率显著低于拮抗剂方案(P<0.05),但两组间获卵数、2PN受精数、2PN卵裂数、囊胚形成率、OHSS率差异无统计学意义。④两组第二次超促排卵新鲜移植周期比较,黄体期长方案新鲜移植率、种植率、临床妊娠率及活产率略高,但差异无统计学意义。首次解冻周期的妊娠结局比较,拮抗剂组的生化妊娠率、临床妊娠率高于黄体期长方案组(P<0.05),但着床率、活产率、新生儿胎龄及出生体质量差异无统计学意义。结论对于首次拮抗剂方案治疗失败的患者,适当增加Gn启动剂量及用量,两种方案均能获得满意的妊娠结局。相较于黄体期长方案,再次使用拮抗剂方案保持了其优势,包括治疗周期短、成本低、患者依从性好。

Pregnancy Outcomes of In Vitro Fertilization with or without Ovarian Hyperstimulation Syndrome： A Retrospective Cohort Study in Chinese Patients

Background： The effect of ovarian hyperstimulation syndrome （OH SS） on pregnancy outcomes of in vitro fertilization （IVF） patients is still ambiguous. Tbis study aimed to analyze pregnancy outcomes of IVF with or without OHSS in Chinese patients. Methods： A retrospective cohort study was undertaken to compare pregnancy outcomes between 190 women with OHSS and 197 women without OHSS. We examined the rates of clinical pregnancy, multiple pregnancies, miscarriage, live birth, preterm deliver）,, preterm birth before 34 weeks＇ gestation, cesarean delivery, low birth weight （LBW）, and small-for-gestational age （SGA） between the two groups. Odds ratios （ORs） and 95% confidence intervals （Cls） of measure of clinical pregnancy were also analyzed. Results： The clinical pregnancy rate of OHSS patients was significantly higher than that of non-OHSS patients （91.8% vs. 43.5%, P 〈 0.001）. After controlling for drug protocol and causes of infertility, the adjusted ORs of moderate OHSS and severe/critical OHSS for clinical pregnancy were 4.65 （95% CI, 1.86-11.61 ） and 5.83 （95% CI, 3.45-9.86）, respectively. There were no significant differences in rates of muhiple pregnancy （4.0% vs. 3.7%） and miscarriage （16.1% vs. 17.5%） between the two groups. With regard to ongoing clinical pregnancy, we also found no significant differences in the rates of live birth （82.1% vs. 78.8%）, preterm delivery （20.9% vs. 17.5%）, preterm birth before 34 weeks＇ gestation （8.6% vs. 7.9%）, cesarean delivery （84.9% vs. 66.3%）, LBW （30.2% vs. 23.5%）, and SGA （21.9% vs. 17.6%） between the two groups. Conclusion： OHSS, which occurs in the luteal phase or early pregnancy in IVF patients and represents abnormal transient hemodynamics, does not exert any obviously adverse effect on the subsequent pregnancy.

Predictive Value of Serum Vascular Endothelial Growth Factor and Pigment Epithelium-derived Factor in Ovarian Hyperstimulation Syndrome

Objective To explore whether the serum concentrations of vascular endothelial growth factor （VEGF） and pigment epithelium-derived factor （PEDF） could serve as the predictors of ovarian hyperstimulation syndrome （OHSS） in patients undergoing in vitro fertilization-embryo transfer （IVF-ET）. Methods Enzyme-linked immunoadsordent assay （ELISA） was employed to measure the serum concentrations of VEGF and PEDF on the day of hCG administration, oocyte retrieval and embryo transfer, respectively. Based on OHSS classification of the criteria of Golan, 85 patients were divided into three groups. Patients in group A （n=10） showed symptoms of severe OHSS and patients in group B （n=13） suffered from moderate OHSS. The control group （group C, n=62） contained patients without symptoms of OHSS as well as patients with mild OHSS.Results In groups A, B and C, serum concentrations of PEDF on the day of hCG administration （h-PEDF）（166.54 ± 102.81 pg/ml, 159.45 ±136. 77 pg/ml, 172.05±170.95 pg/ml, P=0.48）, oocyte retrieval （o-PEDF）（176.91 ± 103.37 pg/ml, 122.52± 92.54 pg/ml, 179.82±177.47 pg/ml, P=0.27） and embryo transfer （e-PEDF）（169.02± 240.08 pg/ml, 136.80 ±139.21pg/ml, 157.38 ±222.54 pg/ml, P=0.95）, h-VEGF （175.55 ± 103.54 pg/ml, 218.84 ±179.70pg/ml, 153.39±145.06 pg/ml, P=0.36） and o- VEGF （171.93 ± 128.55 pg/ml, 220.36±149.82 pg/ml, 138. 74 ±% 139.30 pg/ml, P=0. 15） showed no significant differences. There was a statistical difference in serum concentration of e-VEGF between group A （197.04±156.63 pg/ml） and group C （110.69±49.55 pg/ml）（P=0.008）. The serum level of estradiol showed a positive correlation with the count of large follicles （r=0. 744）. The ratios of h-VEGF/h-PEDF, o-VEGF/o-PEDF and e-VEGF/e-PEDF were calculated and showed a clear difference among groups A, B and C （4.04±3.39, 2.10±2.14, 1.05± 4.80, P〈0.001; 4.54 5.69, 2.29 ±1.67, 0.94 ±0.59, P〈0.001; 5.43±6.16, 1.81±1.36, 2.42±2.60, P=0.04）. Conclusion While neither serum concentrations of VEGF nor PEDF can be used as an OHSS predictor, the ratios of h-VEGF/h-PEDF, o-VEGF/o-PEDF and e-VEGF/e-PEDF may have great predictive value.

Effects of gonadotropin-releasing hormone antagonists on the expression of vascular endothelial growth factor and its receptors in a rat model of ovarian hyperstimulation syndrome

Background Ovarian hyperstimulation syndrome （OHSS） is one of the most life-threatening complications of assisted reproduction treatments. Gonadotropin-releasing hormone antagonists （GnRHanta） are thought to be effective in preventing this complication, and some clinical trials have found lower incidences of OHSS in patients treated with GnRHanta. Our aim was to investigate the effects of GnRHanta on vascular permeability and the expression of vascular endothelial growth factor （VEGF） and its receptors in a rat model of OHSS. Methods An immature early OHSS rat model was established. Three ovarian stimulation protocols were used： pregnant mare serum gonadotropin/human chorionic gonadotropin （hCG） alone, with a GnRHanta, or with a gonadotropin-releasing hormone agonists （GnRHa）. Blood and tissue samples were collected at 48 hours after hCG administration. Vascular permeability was evaluated by measuring the Evans-Blue content of extravasated peritoneal fluids. The expression of VEGF and its receptors, including fit-1 and KDR, were detected by reverse transcriptase-polymerase chain reaction and Western blotting. Results Treatment with both a GnRHanta and a GnRHa resulted in significant reductions in serum estradiol and peritoneal vascular permeability, as well as decreased ovarian expression of VEGF and its two receptors. However, GnRHanta treatment caused a greater reduction in serum estradiol concentrations, and in VEGF receptor mRNA expression than GnRHa. There were no significant reductions in the expression of VEGF or its receptors in extra-ovarian tissues, including the liver, lungs and peritoneum. Conclusion Our results reveal that GnRHanta are more potent than GnRHa in preventing early OHSS through down-regulation of the expression of VEGF and its receptors in hyperstimulated ovaries.