不同剂量来曲唑预防早发型卵巢过度刺激综合征的临床研究

目的:探讨卵巢过度刺激综合征(OHSS)高危患者在取卵后应用不同剂量来曲唑(LE)预防早发型OHSS发生的效果。方法:88例患者随机分为4组,A~C组为LE组,取卵即日起每日添加LE,LE剂量分别为A组(n=21)2.5 mg/d,B组(n=23)5.0 mg/d,C组(n=20)7.5 mg/d,D组为对照组(n=24)。测患者黄体期内分泌、血管内皮细胞生长因子(VEGF)水平及中重度OHSS发生率。结果:h CG注射后第5日始血清E_2水平随时间变化呈降低趋势,随着LE剂量增加,E_2水平降低速度明显加快,组间差异有统计学意义(P0.05)。血清LH水平在注射h CG后第8日、第10日随着LE剂量的增加而逐渐上升,P水平却逐渐降低,组间差异显著(P0.05)。血清VEGF水平从h CG注射后5日始,D组呈上升趋势,而其它三组呈下降趋势,随着LE剂量的增加,血中VEGF水平越低,各组之间两两比较,差异均具有统计学意义(P0.001)。C组中重度OHSS发生率低于D组。结论:不同剂量的LE均能一定程度降低血清E_2及VEGF水平,当剂量增至7.5 mg/d时,OHSS发生率最低。     

Severe ovarian hyperstimulation syndrome after combined GnRH-agonist and low-dose human chorionic gonadotropin trigger in a patient with a single kidney

Ovarian hyperstimulation syndrome (OHSS) following gonadotropin-releasing hormone agonist (GnRH-a) trigger is rare. Here, we report a case of severe OHSS after combined GnRH-a and low-dose human chorionic gonadotropin (hCG) trigger in a patient with a single kidney. The patient is a 32-year-old women with a two-year history of infertility. The patient’s history was significant for a single kidney, that is, she had donated a kidney to a family member three years ago. The patient underwent controlled ovarian stimulation (COS) for in vitro fertilization (IVF) and received a combined 2?mg GnRH-a and 1500?IU hCG ovulatory trigger. Estradiol (E₂) levels on the day of and after the trigger were 3800?pg/mL and 4001?pg/mL, respectively. Four days after the trigger, the patient began experiencing nausea, abdominal distention and dyspnea, and her blood testing revealed hemoconcentration (hemoglobin: 16.9?g/dL; hematocrit: 51.0%) and an elevated creatinine level (1.16?mg/dL). Fresh embryo transfer was deferred. The patient was admitted to the hospital for fluid monitoring and prophylactic anticoagulation. Following inpatient management, her hemoglobin, hematocrit and creatinine levels normalized. The current report highlights that the systemic effects of OHSS can be accentuated in patients with preexisting renal disease or a single kidney.     

Why more is less and less is more when it comes to ovarian stimulation

PurposeThe purpose of the present study is to describe the possible mechanisms which may explain the apparent paradox of “less is more.” Mild ovarian stimulation for in vitro fertilization (IVF) minimizes ovarian hyperstimulation syndrome (OHSS) and multiple gestations without compromising the pregnancy rate (PR).MethodsThe pertinent English literature (PubMed) addressing mild stimulation for IVF/assisted reproductive technology (ART) and publications addressing “mild” or “soft” controlled ovarian stimulation (COS) vs conventional COS for IVF, OHSS, natural cycle IVF, and IVF outcome in association with COS was searched.ResultsFour possible mechanisms can be put forward to explain the apparent paradox of “less is more.” (1) In the natural or mild stimulation cycles, the healthiest follicles are selected by the principle of “quality for quantity”; (2) high estradiol (E₂) in the late follicular phase significantly correlated with higher rates of small for gestational age (SGA) and low-birth-weight (LBW) neonates; (3) anti-Mullerian hormone (AMH), LH, testosterone, and E₂ are significantly higher in natural cycle (NC)-IVF than in stimulated IVF follicles, suggesting an alteration of the follicular metabolism in stimulated cycles; and (4) supraphysiological E₂ may increase the growth hormone-binding protein (GH-BP) bio-neutralizing GH and diminishing the resultant insulin-like growth factor (IGF) levels, necessary for optimal synergism with follicle-stimulating hormone (FSH).ConclusionsIt is suggested to aim at the retrieval of around eight to ten eggs. Mild stimulation should be the common practice for IVF. In cases where more than ten ova are retrieved or high E₂ levels are reached, either intentionally or unintentionally, “freeze-all policy” should be considered and embryo transfer (ET) done in a subsequent natural cycle.     

妊娠合并系统性红斑狼疮患者孕期并发症及妊娠结局的临床分析

目的分析并探讨系统性红斑狼疮(SLE)患者的孕期并发症情况及妊娠结局。方法回顾性分析2000年1月至2010年3月北京大学人民医院收治的19例妊娠合并SLE患者的临床资料,对影响SLE合并妊娠并发症的相关因素和SLE不同妊娠时机的妊娠结局进行分析。结果 19例患者中11例(11/19,57.9%)出现了母儿并发症,4例重度子痫前期,1例流产,2例死胎,2例足月低出生体重,4例早产。无并发症组8例,两组患者的孕产次及孕前病程、分娩方式无明显差异,但无并发症组患者的年龄小于并发症组,分娩孕周明显延长,新生儿体重明显增加,两组差异有统计学意义(P=0.006);孕前病情的稳定程度对孕期母儿并发症的影响差异无统计学意义(P=0.633);但妊娠前病情稳定大于6个月的患者出现并发症的比例较低(6/12,50.0%vs5/7,71.4%)。3例妊娠期间诊断SLE的患者均在孕期或产后出现了严重的并发症,1例(1/3,33.3%)新生儿诊断为SLE;与孕前病情控制平稳6个月的患者相比,分娩孕周较小,新生儿体重较低(P0.05)。结论 SLE患者即使孕前病情控制平稳,妊娠后仍有可能出现严重的母儿并发症。在病情控制平稳后妊娠,孕期在产科和风湿科医师的共同严密监测下,坚持治疗,适时终止妊娠是改善母婴结局的关键。同时应注意提高对妊娠期SLE的诊断。     

改良GnRH-a长方案在控制性促排卵中的应用

目的探讨改良GnRH—a/FSH/hMG联合长方案在控制性促排卵中的应用以及国产阿拉瑞林在此方案中的使用。方法以回顾性分析的方法对174例改良GnRH-a长方案和48例超短方案控制性促排卵的资料进行回顾性分析。结果 改良GnRH—a/FSH/hMG联合长方案在FSH/hMG用药天数、用药量、取卵数、移植数、冻存胚胎数、hCG丑内膜厚度、临床妊娠率、种植率、流产率、OHSS发生率等方面与短方案组相比差异均无显著性(P>0.05),其中流产率明显低于超短方案组。结论改良国产阿拉瑞林/FSH/hMG联合长方案是一种简单、经济、有效的控制性促排卵方案,值得在IVF—ET周期中推广。     

Preeclampsia in pregnancies complicated by systemic lupus erythematosus (SLE) nephritis: prophylactic treatment with multidisciplinary approach are important keys to prevent adverse obstetric outcomes

Introduction: Systemic lupus erythematosus (SLE) commonly affects women of childbearing age. Hypertension, antiphospholipid syndrome, and lupus nephritis are risk factors for adverse maternal/fetal outcome. The aim of this retrospective cohort study is to compare pregnancy outcomes in patients with and without SLE nephritis, using a multidisciplinary approach and a broad prophylaxis protocol.

Materials and methods: Data were collected from 86 pregnancies complicated by SLE. Twenty-seven women with nephropathy before pregnancy stated as the study group and 59 formed the control group. Each group received a prophylactic treatment based on their clinical characteristics. Results were expressed as mean?±?SD, percentage and χ²-test (significant values when p?Results: The prophylactic treatment (60.4% of the patients) significantly controlled the complications related to some risk factors, such as antiphospholipid antibodies (aPL) and nephritis. Preeclampsia occurred in 14.8% of patients. Patients with pregestational hypertension showed a 2.75 odds ratio of adverse events when compared to the group without chronic hypertension. The presence of proteinuria was associated with a risk of preeclampsia 2.45 times greater, as well as serum creatinine >1.2?mg/dL, which was related to a risk 1.25 times higher than the risk observed in patients with serum creatinine <1.2?mg/dL. A 6-month inactive disease was associated with a better outcome. A value of Estimated Glomerular Filtration Rate (eGFR)?2 resulted in a 18.73 times greater risk of preeclampsia, intrauterine growth restriction (IUGR), and preterm delivery.

Discussion: A multidisciplinary approach in a tertiary care center and a broad prophylactic treatment protocol to patients affected by SLE and complicated by nephritis may definitively foster a successful pregnancy.     

Early timed follicular aspiration prevents severe ovarian hyperstimulation syndrome

Purpose: Early timed follicular aspiration (ETFA) of one ovary 10–12 hr after administration of chorionic gonadotropin (hCG) is an attempt to prevent severe ovarian hyperstimulation syndrome (OHSS). After the introduction of early timed follicular aspiration ETFA of one ovary in IVF/ET cycles at high risk for severe OHSS, no cases of severe OHSS were registered in the Ljubljana IVF/ET program. In the period before preventive ETFA (1984–1992) there were 16 cases of severe OHSS of 4798 IVF/ET cycles followed by 577 clinical pregnancies. After the introduction of ETFA (1992–1993) there were no cases of severe OHSS of 2289 IVF/ET cycles followed by 364 clinical pregnancies. Methods: We attempted to evaluate the significance of this observation by comparing two groups of female infertility IVF/ET cycles at high risk for severe OHSS. The occurrence of severe OHSS and clinical parameters in the two groups of IVF/ET cycles at high risk for severe OHSS were compared. Results: In the group of 106 IVF/ET female infertility cycles at high risk of severe OHSS with preventive ETFA, there were no cases of severe OHSS. In the control group of 92 IVF/ET female infertility cycles at high risk for severe OHSS with normally timed follicular aspiration (NTFA) of both ovaries, severe OHSS occurred in 16 cases. The difference in the occurrence of severe OHSS between the two groups is highly significant (P<0.005), both in hMG/hCG- and in GnRHa/hMG/hCG-induced IVF/ET cycles. No difference in live birth rate (16 vs. 16%) between the two groups was noted. Conclusions: Considering these results we conclude that ETFA is another successful option to decrease the incidence of severe OHSS in assisted reproduction. The preventive effect of follicular aspiration seems to depend on its timing.     

卵巢慢反应患者控制性超促排卵相关因素分析:一项多中心回顾性研究

目的探讨控制性超促排卵(COH)过程中发生卵巢慢反应可能的相关因素。方法回顾性分析2014年1月—2016年1月期间于兰州大学第一医院、新疆佳音医院、青海省人民医院、银川市妇幼保健院、广西玉林市妇幼保健院进行促性腺激素释放激素激动剂(GnRH-a)长方案体外受精-胚胎移植(IVF-ET)的144例卵巢慢反应患者的临床资料,与132例卵巢正常反应患者(正常对照组)进行对比。结果与正常对照组相比,慢反应组患者体质量指数(BMI)、促甲状腺激素(TSH)较高,降调节及促排卵时间较长,促性腺激素(Gn)使用后7d平均卵泡直径偏小,雌二醇(E_2)、黄体生成素(LH)低,hCG注射日E_2低,IVF双原核(2PN)卵裂率较高,临床妊娠率低,差异均有统计学意义(P0.05)。患者年龄、不孕年限、基础卵泡刺激素(FSH)、LH、催乳素(PRL)、E_2、基础卵泡数、hCG注射日孕酮(P)、获卵率、胚胎质量、胚胎种植率、流产率、宫外孕率、继续妊娠率及取消移植率组间均无统计学差异(P0.05)。结论卵巢慢反应可能与患者BMI过高、甲状腺功能降低及GnRH-a过度抑制相关,较长的Gn天数仍可使慢反应患者获得较好的妊娠结局。     

Ovarian hyperstimulation syndrome is associated with reversible impairment of vascular reactivity

OBJECTIVE: To determine if there is a loss of normal peripheral arteriolar vasoconstrictor reactivity in women with severe ovarian hyperstimulation syndrome (OHSS). SETTING: Prospective controlled study. DESIGN: National University Hospital, Singapore. PATIENT(S): Forty-three women undergoing treatment in an IVF program: 22 women with severe OHSS and 21 normal women without OHSS. INTERVENTION(S): Measurement and quantification of the cutaneous arteriolar vasoconstrictor response using laser Doppler fluximetry. MAIN OUTCOME MEASURE(S): Changes in blood flow as an index of vasoconstrictor response before and after treatment for OHSS with albumin. RESULT(S): The mean (+/-SE) percentage (%) change in normal control women was -68.3% +/- 4.7. This was significantly different from women with OHSS (-32.3% +/- 11.1). The response in women with OHSS changed significantly after treatment with IV albumin (-60.4% +/- 5.7) and was no different than the control response. The reproducibility of the technique was -13.6% (+/-2.8). CONCLUSION(S): Women with OHSS have impaired vascular reactivity when compared with normal women.     

血清及卵泡液中抑制素B动态变化及其与促排卵结局的相关性研究

目的:探讨不同控制性超促排卵(controlled ovarian hyperstimulation,COH)方案中血清及卵泡液(follicular fluid,FF)中抑制素B(inhibin B,INHB)的动态变化及其与COH结局的相关性。方法:收集因输卵管因素和/或男方因素首次接受体外受精/卵细胞质内单精子注射-胚胎移植(IVF/ICSI-ET)助孕患者COH过程各时间节点的血清及取卵(ovum pick up,OPU)日不同大小卵泡的FF,按筛选要求选取长方案组(A组,n=38)及非降调节方案组(B组,n=38)患者,对其血清及FF中INHB水平进行检测并行相关性分析。结果:①降调节过程中,血清INHB水平显著下降(P0.01),且Gn启动日A组血清INHB水平较B组明显下降(P=0.000)。②A组和B组Gn启动后血清INHB水平呈上升趋势,至h CG注射日达高峰后下降,OPU后2 d显著下降(P0.01);A组和B组基础及Gn启动后的血清INHB水平无统计学差异(P0.05)。③ Gn第5日血清INHB水平与COH结局相关性最强,且Gn启动日血清INHB水平与Gn用量呈高度负相关(P0.01)。④A组和B组FF中血清INHB水平随卵泡直径增大而升高,大卵泡的FF中INHB水平无统计学差异(P0.05),但A组中小卵泡的FF中INHB水平显著高于B组(P0.01);且大卵泡的FF中INHB水平与COH结局相关性最好。结论:①降调节后血清INHB水平预示降调节对卵泡同步化作用较好;②COH过程中血清及大中卵泡的FF中INHB水平能很好地预测卵巢反应性及COH结局。     

Relationship between human chorionic gonadotropin serum levels and the risk of ovarian hyperstimulation syndrome

The object of this retrospective cohort study was to determine if hCG levels correlate with ovarian hyperstimulation syndrome (OHSS) risk after adjustment for other risk factors during in vitro fertilization (IVF). We measured serum hCG approximately 12?h after hCG trigger in women undergoing 406 cycles of controlled ovarian hyperstimulation for IVF between June 2006 and December 2009. Serum hCG levels were measured 12?h after trigger. Bivariate logistic regression was used to assess the association between patient and cycle characteristics and OHSS. In our series, mild to moderate OHSS occurred in 9% (38/406), and severe OHSS diagnosed in 1.5% (6/406) of IVF cycles. OHSS risk was increased in younger women (<30 years old: adjusted odds ratio: aOR 2.46, 95% confidence interval: CI 1.14–5.34), increased number of oocytes (11–20: aOR 6.79, 95% CI 1.97–23.40; >20: aOR 17.55, 95% CI 4.84–63.70), and increase E₂ levels (≥3,000?pg/mL: aOR 2.59, 95% CI 1.33–5.05), but was unrelated to hCG level (100–200?IU/L: aOR 1.53, 95% CI 0.60–3.91; ≥200?IU/L: aOR 1.42 95% CI 0.48–4.20). These results indicate that OHSS risk during IVF is unrelated to serum hCG level measured approximately 12?h after trigger.     

三种助孕技术治疗多囊卵巢综合征不孕的疗效比较

目的：观察３种助孕技术：ＩＶＦ ＥＴ、ＧＩＦＴ和控制性超促排卵（ＣＯＨ）后自行同房对多囊卵巢综合征（ＰＣＯＳ）不孕患者的疗效。方法：应用３种方法治疗,观察各组的临床妊娠率和发生卵巢过度刺激综合征（ＯＨＳＳ）的情况。结果：ＩＶＦ ＥＴ和ＧＩＦＴ与ＣＯＨ相比能得到更高的临床妊娠率,而前二者发生ＯＨＳＳ的危险性明显低于后者。结论：为避免ＣＯＨ后发生ＯＨＳＳ,建议对因ＰＣＯＳ不孕的患者采取体外助孕技术治疗。应用何种技术要根据患者的具体情况而定。如果有至少１ 条输卵管完全正常,可先试行ＧＩＦＴ。此外,须将多余的卵子进行体外授精试验,观察其受精及卵裂情况,从而对今后的治疗提出指导性建议,并要将得到的胚胎进行冷冻保存,以备今后使用。     

Symposium

This study aims to provide an estimate of women's risk of ovarian hyperstimulation syndrome (OHSS) when undergoing superovulation to donate eggs for research. This is an essential prerequisite for appropriate informed consent. In the absence of sufficiently large numbers of egg donors to assess the risk, comparative data was obtained from women undergoing the same superovulation protocol for in vitro fertilization (IVF) treatment. In this prospective study 339 women, who developed ≥20 follicles after superovulation in their first treatment cycle (total number of treatment cycles during the same period – 2417), were intensively monitored on five occasions, between human chorionic gonadotrophin and pregnancy test, according to our routine clinical protocol. Hospital admission was needed for 49 (14.5%) women, 13 (3.8%) needed intravenous fluids and 9 (2.7%) needed paracentesis. The admission rates were similar in pregnant and non-pregnant women (13.5% vs. 15%); the need for intravenous fluids and paracentesis were 3.2% vs. 2.3% and 6.3% vs. 2.3%, respectively. The peak increase in haematocrit occurred on Day 4 after hCG, and the mean day of hospital admission was Day 5. If an egg donor develops <20 follicles, she can be reassured that the risk of OHSS is very small (<0.1%). If ≥20 follicles develop, her risk of hospital admission due to OHSS is <15%. The absence of pregnancy in egg donors does not eliminate the risk of OHSS. Given the timescale of development of the haematological and biochemical abnormalities, egg donors who develop ≥20 follicles should be actively monitored for the first week after egg collection.     

Comparison of cabergoline versus calcium infusion in ovarian hyperstimulation syndrome prevention: A randomized clinical trial

Aim

To compare effectiveness of calcium infusion (CI) versus oral cabergoline (OC) in lowering the incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high risk women undergoing in vitro-fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles.

Obstetric outcome of in vitro fertilized pregnancies complicated by severe ovarian hyperstimulation syndrome: a multicenter study

Objective: To assess the outcome of pregnancies conceived with the use of IVF that are complicated by severe ovarian hyperstimulation syndrome (OHSS).

Design: A retrospective nationwide multicenter study.

Setting: Sixteen of 19 tertiary care medical centers in Israel.

Patient(s): All patients undergoing IVF who were hospitalized for severe OHSS between January 1987 and December 1996.

Main Outcome Measure(s): Pregnancy rate (PR) and rates of multiple gestation, miscarriage, ectopic pregnancy, obstetric complications, and intervention.

Result(s): A total of 163 patients who had severe OHSS after IVF treatment were identified, of whom 142 (87.1%) had undergone ET. The clinical PR was 73.2%; 42.3% were singletons, 33.6% were twins, 17.3% were triplets, and 6.7% were quadruplets. The miscarriage rate was 29.8%, whereas the incidence of ectopic pregnancy was 1.9%. Forty-four percent of all births were premature, and 62.1% of all newborns had low birth weight. The most common antenatal complications were pregnancy-induced hypertension (13.2%), gestational diabetes (5.9%), and placental abruption (4.4%). The rate of cesarean section was 44.1%.

Conclusion(s): Among patients who have severe OHSS after IVF treatment, the pregnancy rate and the rates of multiple gestation, miscarriage, prematurity, low birth weight, pregnancy-induced hypertension, gestational diabetes, and placental abruption are significantly higher than those reported previously for pregnancies conceived with the use of assisted reproductive techniques.     

Ovarian cyst aspiration prior to initiating ovarian hyperstimulation for in vitro fertilization

Twenty-three consecutive patients presenting for in vitro fertilization were evaluated with transvaginal sonography on cycle day 3, prior to initiating ovarian hyperstimulation. Three of these patients were noted to have large ovarian cysts. All three underwent transvaginal aspiration of the cysts, followed immediately by initiation of ovarian hyperstimulation. Following oocyte retrieval, in vitro fertilization, and embryo transfer, all three women achieved pregnancy. We conclude that cyst aspiration is not contraindicated when an ovarian cyst is encountered in the follicular phase of an in vitro fertilization cycle.