Effect and Underlying Mechanism of Bu-Shen-An-Tai Recipe on Ovarian Apoptosis in Mice with Controlled Ovarian Hyperstimulation Implantation Dysfunction

The effect and underlying mechanism of Bu-Shen-An-Tai recipe on ovarian apoptosis in mice with controlled ovarian hyperstimulation(COH) implantation dysfunction were studied. The COH implantation dysfunction model in mice was established by intraperitoneal injection of 7.5 IU pregnant mare’s serum gonadotrophin(PMSG), followed by 7.5 IU human chorionic gonadotrophin(HCG) 48 h later. Then the female mice were mated with male at a ratio of 2:1 in the same cage at 6:00 p.m. The female mice from normal group were injected intraperitoneally with normal saline and mated at the corresponding time. Day 1 of pregnancy was recorded by examining its vaginal smears at 8:00 a.m. of the next day. Fifty successfully pregnant mice were equally randomly divided into 5 groups: normal control pregnant group(NC), COH implantation dysfunction model group(COH), low dosage of Bu-Shen-An-Tai recipe group(LOW), middle dosage of Bu-Shen-An-Tai recipe group(MID) and high dosage of Bu-Shen-An-Tai recipe group(HIGH). Then from day 1, the mice in different groups were respectively intragastrically given corresponding treatments at 9:00 a.m. for 5 consecutive days. The concentrations of 17β-estradiol(E) and progesterone(P) were determined by radioimmunoassay(RIA). The ultrastructural changes of ovarian tissues were observed by transmission electron microscope(TEM). The histopathological changes of ovarian tissues were observed by HE staining. The number of atretic follicles and pregnant corpus luteum were also recorded. TUNEL was applied to measure apoptotic cells of ovarian tissues. Western blotting was used to detect the protein expression of apoptosis-related factors like Bax, Bcl-2 and cleaved-caspase-3 in ovarian tissue of mice. The results showed that ovarian weight, the concentrations of Eand P, the number of atretic follicles and pregnant corpus luteum, as well as the apoptosis of granulosa cells were significantly increased in the COH group. The ultrastructures of ovarian tissues in the COH group showed that chromatin in granulosa cells was increased, agglutinated, aggregated or crescent-shaped. The focal cavitation and the typical apoptotic bodies could be seen in granulosa cells in the late stage of apoptosis. After the treatment with different doses of Bu-Shen-An-Tai recipe, the ultrastructural changes of ovarian granulosa cells apoptosis were dramatically improved and even disappeared under TEM. Visible mitochondria and mitochondrial cristae were increased and vacuoles were significantly reduced. The lipid dropltes were shown in a circluar or oval shape. The protein expression levels of Bax and cleaved-caspase-3 were decreased, and the expression of Bcl-2 protein was increased after treatment. It was concluded that Bu-Shen-An-Tai recipe can inhibit the apoptosis of ovarian granulosa cells, probably by up-regulating the protein expression of Bcl-2 and down-regulating Bax and cleaved-caspase-3, which contributes to the formation and maintenance of ovarian corpus luteum. It’s helpful to promote the embryonic implantation, to reduce embryo loss and ultimately to improve the success rate of pregnancy.

Endometrial Mucin-1 and Pinopode in Peri-implantation Phase in Ovarian High Responders during Controlled Ovarian Hyperstimulation Cycles

Objective To investigate effects of ovarian high response on endometrial mucin-1 （MUC1） and pinopode in peri-implantation phase in controlled ovarian hyperstimulation （COH） cycles. Methods Ovarian high response was defined as serum E2 〉 15 000 pmol/L on the day of hCG administration in COH cycle using GnRH agonist and recombinant FSH （n=8）. Healthy and fertile women were used as the natural control （n=10）. Endometrial biopsies were performed on the day of LH＋ 7/hCG＋ 7. Pinopode formation was observed by scanning electron microscope. Expression of MUC1 was detected with quantitative Real-time PCR and immunohistochemistry. Results In high response group, the lumen surface was covered with variant pinopodes and microvillous. The expression of MUC1 mRNA in high response group was lower than that in the natural control （P〈0.05）. Immunostaining for MUC1 protein in glandular and luminal epithelium in high response group was lower than that in the natural control （P〈0. 05）. Conclusion Asynchronized pinopode appearance and lower expression of MUC1 during peri-implantation period were the characteristics of endometrium in high response group, Which may provide a clue of decreased endometrial receptivity in the supraphysiological hormone milieu.

Missed estradiol determination resulting in oocyte retrieval and embryo development following controlled ovarian hyperstimulation at early pregnancy: Case report

This paper is a case report on the success of oocyte retrieval and good quality embryo development following controlled ovarian hyperstimulation at early pregnancy. A 30-year-old patient underwent controlled ovarian hyperstimulation by gonadotropin-releasing hormone agonist long protocol. On the day of oocyte collection, a 5-week gestational sac was observed by exact sonography monitoring. However, via ultrasound guided follicle puncture, 7 oocytes were collected. After intarcytoplasmic sperm injection, 3 developed good quality embryos were cryopreserved. Moreover, the natural pregnancy was continued and finally a healthy live birth was achieved. Despite physiological hormonal changes during pregnancy, the follicular growth occurred and followed by oocyte retrieval and embryo development, subsequently.

Pharmacotherapy Cost of Controlled Ovarian Hyperstimulation of <i>in Vitro</i>Fertilization—A Real Life Study

The aim of the current study is to analyze the cost of controlled ovarian hyperstimulation (COH) of in vitro fertilization (IVF) during the period 2009-2013 in a specialized gynecology clinic. It is a prospective, observational study and bottom up cost analysis of the COH pharmacotherapy of IVF. The data was collected for all women admitted to the clinic, therapeutic COH protocols, prescribed medicines and doses, average length of therapy and its cost. Statistical analysis is applied towards the pharmacotherapy and cost data. On average 136 (SD 21.92) women were admitted varying from 105 to 179 for 10.7 (SD 1.47) days. 11% were on long (GnRH agonist containing) therapeutic COH protocol and all other on short (GnRH antagonist containing). Therapeutic protocols include Follitropin-α IU (103 women at average dose of 1171 IU (SD 314.16));Follitropin-β IU (299 women at average dose of 1634 IU (SD 423.5));Urofollitropin 75 IU amp (243 women at average dose of 21.3 IU (SD 7.37));urFSH + urLH 75IU:75IU/amp (354 women at average dose of 23.4 IU (SD 8.8));cetrorelix amp 0.25 mg prescribed at 264 women at average dose of 3.84 IU (SD 1.32);ganirelix amp 0.25 mg for 299 women at average dose of 4.01 mg (SD 1.32);Human chorion gonadotropin for 535 women at average dose of 6752.52 IU (SD 1216.23);Nafarelin mcg/ml for 8 women at dose of 17,700 mcg (SD 10,725);triptorelinacetat 0.1 mg amp - 63 women at doses of 5.5 (SD 3.25) mg at 14 women and average dose of 7.5 mg (SD 2.5);clomiphen citrate and letrozole for 15 women at average dose of 8 mg (SD 2.4). The average cost of COH pharmacotherapy is varying among the years with highest value of 1803.776 (SD - 624.89) BGN in 2009. Controlled ovarian hyperstimulation of in vitro fertilization is cost and resource consuming procedure in regards to pharmacotherapy. Age and reason of infertility influence significantly the cost.

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.

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。

Yiqixue Buganshen Recipe(益气血补肝肾方) Regulates the Expression of Integrin ανβ 3 in the Endometrium of Controlled Ovarian Hyperstimulation Mice

Objective： To observe the effect of Yiqixue Buganshen recipe （益气血补肝肾方, YBR） on the expression of integrin e~ v 13 3 in the endometrium of controlled ovarian hyperstimulation mice. Methods： A total of 180 mice were divided into three groups： model group, treatment group and control group. The treatment and model groups were intraperitoneally injected with gonadotropin-releasing hormone analogue for 7 days; pregnant mare serum gonadotropin was also injected on the 7th day. After 48 h, human chorionic gonadotropin was injected. The control group was injected with an equal volume of saline at the same time. From the start of the experiment, the treatment group was intragastrically administered Jinghouzengzhi Recipe （经后增殖方） and Cuhuangti Recipe （促黄体方）. The model group and the control group were intragastrically administered an equal volume of saline. Real-time reverse transcription polymerase chain reaction and Western blotting were used to detect the mRNA and protein expression of integrin α υ β 3 in mouse endometrium. Results： Integrin α υ β 3 was expressed in mouse endometrium in all groups. Integrin α υ β 3 expression increased gradually along with pregnancy, progressing from pregnant day （Pd） 1. Integrin α υ β 3 expression significantly increased on Pd 4, then began to decrease on Pd 6. Integrin α υ β 3 expression in the treatment group was higher than in the model group, and the difference was statistically significant （P〈0.05）. The difference between the treatment group and the control group was not statistically significant （P〉0.05）. Conclusion： YBR improves endometrial receptivity, and may play an important role in embryonic implantation.

Effects of Er'zhi Tiangui Granule (二至天癸颗粒) on Sequential Expressions of Integrin β3 and Its Ligand Osteopontin in Mouse Endometrium during Controlled Ovarian Hyperstimulation

To investigate the effects of ECzhi Tiangui Granule （二至天癸颗粒, ETG） on sequential expressions of integrin β 3 and its ligand osteopontin in the mouse endometrium during controlled ovarian hyperstimulation （COH） and implantation period. Methods： Seventy-five Mature female Kunming mice were randomly divided into 3 groups, a normal control group, a model group, and a treatment group administrated with ETG for 10 days, 25 in each group. After mated with male mice, every 5 mice were sacrified in each group at the 0, 2nd, 4th, 6th, and 8th days to take their endometrium. In-situ hybridization was used to detect the expressions of integrin β 3 and osteopontin in the endometrium. Results： mRNA expressions of integrin β 3 and osteopontin in the endometrium during implantation period showed similar time sequence rules in the treatment group to those in the normal control group; the peak values of them were a little lower in the treatment group than the normal control without significant differences. In the model group, integrin β 3 mRNA expression was higher at the 2nd day, obviously lower at the 4th and 6th days, and insignificantly lower at the 8th day; and osteopontin expression was remarkably lower at the 4th, 6th, and 8th days, compared with the normal control and the treatment groups （P〈0.05, P〈0.01）. Conclusions： COH might influence the sequential expressions of integrin β 3 and its ligand osteopontin, bring forward the integdn β 3 expression peak, impact on the cooperation of integrin β 3 and osteopontin, so as to damage the endometrial receptivity. ETG could regulate the sequential expressions of integrin β 3 and its ligand osteopontin to improve the mouse endometrial receptivity during COH.

控制性超促排卵对子宫内膜的影响

控制性超促排卵(controlled ovarian hyperstimulation,COH)是辅助生殖技术的重要组成部分,可显著提高体外受精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)的妊娠率。尽管COH在促进卵泡发育和获取卵母细胞数量方面可获得明显的益处,并能够选择高质量的胚胎进行移植,但COH可能涉及种植窗、子宫内膜容受性、孕酮和雌二醇以及子宫收缩功能的改变,影响不孕患者的胚胎种植率和IVF妊娠率。本文就COH后子宫内膜变化的病理生理机制进行综述,以更好地解决不孕症临床治疗的瓶颈问题。

经后增殖方对控制性超促排卵大鼠卵巢GDF9分泌及颗粒细胞凋亡的影响

目的观察益气血法经后增殖方通过p38MAPK/CK2/IκBα/NF-κB通路对控制性超促排卵(COH)大鼠卵巢GDF9分泌及颗粒细胞(GCs)凋亡的影响。方法建立COH大鼠模型,18只大鼠随机分为自然排卵组(NO组)、COH组、COH+经后增殖方组(COH+JHZZG组)。qRT-PCR和Western blot法检测p38MAPK、CK2、IκBα、NF-κB、GDF9 mRNA和蛋白的表达水平,TUNEL法检测卵巢GCs凋亡率。结果与NO组比较,COH组大鼠卵巢组织p38MAPK、NF-κB表达升高,CK2、IκBα、GDF9表达下降,卵巢GCs凋亡率升高,差异有统计学意义(P<0.01);与COH组比较,COH+JHZZG组大鼠卵巢组织p38MAPK、NF-κB表达下降,CK2、IκBα、GDF9表达升高,差异有统计学意义(P<0.01);卵巢GCs凋亡率下降,差异有统计学意义(P<0.05)。结论益气血法经后增殖方通过p38MAPK/CK2/IκBα/NF-κB通路促进COH大鼠卵巢GDF9的分泌,抑制卵巢GCs的凋亡,从而提高COH卵细胞质量。

补充褪黑素的人卵母细胞体外培养成熟技术在COH周期中的应用

目的比较同一控制性超促排卵(COH)治疗周期中,体内成熟与改良技术体外培养成熟(IVM)的卵母细胞的早期胚胎发育能力及临床结局,探讨补充褪黑素的IVM技术在临床中的应用。方法收集159例患者在COH周期中的920个成熟卵母细胞进行常规体外受精(IVF/ICSI)处理,同时收集同周期中1283个未成熟卵母细胞,在添加褪黑素的改良IVM培养基中培养成熟后行ICSI处理。通过回顾性分析,比较常规助孕技术与改良IVM技术这两种方式,对辅助生殖治疗的助孕结局和妊娠结局的影响。结果与从COH周期中收集到的行常规IVF/ICSI处理的成熟卵母细胞相比,经改良IVM技术促成熟的卵母细胞的优质囊胚形成率较低。但经胚胎移植后,两种方式获得的成熟卵母细胞的临床结局包括临床妊娠率、足月产率、婴儿体长、新生儿Apgar评分,差异均无统计学意义。结论IVM可以提高从COH周期中回收的未成熟卵母细胞的卵子利用率,改善辅助生殖技术助孕患者的妊娠结局。

Association of Thr307Ala and Asn680Ser of Follicle-Stimulating Hormone Receptor Gene Polymorphisms with Gonadotropin Administration during Controlled Ovarian Hyperstimulation

Objective:This study is to investigate the effect of different single-nucleotide polymorphisms of follicle-stimulating hormone receptor(FSHR)gene on gonadotropin(Gn)administration dosage during controlled ovarian hyperstimulation(COH)protocol of in vitro fertilization and embryo transfer.Methods:This retrospective study included 184 Chinese infertile women in Center for Reproduction and Genetics of Suzhou Municipal Hospital from June 2012 to 2014.All of the enrolled patients were homogeneous in some basal characteristics,and they all met the eligibility criteria.Blood tests were conducted on day 3 of menstrual cycle or the day of human chorionic gonadotropin administration for hormonal profile analysis and DNA extraction.DNA sequencing was performed for polymorphism analysis.The participants were classified into threonine(Thr)/Thr,Thr/alanine(Ala),and Ala/Ala groups according to genotype at position 307,and asparagine/asparagine(Asn/Asn),Asn/serine(Ser),and Ser/Ser groups according to genotype at position 680.Logistic regression and correlation analyses were performed to identify the effect of these two polymorphisms on Gn consumption.Results:The frequency of Thr307Ala and Asn680Ser distribution was consistent with Hardy-Weinberg equilibrium(P>0.05).No significant difference was found in age,basal hormone levels for different genotype groups.Logistic regression analysis results revealed that patients with Ser680Ser genotype have a higher risk of requiring a high dose of Gn compared with patients with Asn680Asn genotype,while polymorphism of Thr307 Ala has no such effect.Conclusion:This study suggested that FSHR genotype Asn680Ser would be helpful in determining the dosage of Gn in COH;patients with Ser680Ser genotype may require higher dose of Gn.

两种重组人卵泡刺激素注射液在不同人群中的促排卵效果分析

目的探究具有不同糖修饰谱的两种重组人卵泡刺激素(rFSH)在不同人群中行控制性促排卵(COH)临床应用的有效性和安全性。方法回顾性分析2022年1—12月期间本中心的320个COH周期的临床资料,按照COH中使用的rFSH种类不同分为A组(芳乐舒,95个周期)和B组(Puregon,225个周期)。比较两组患者在起始剂量、刺激时间、HCG日激素水平和内膜厚度、获卵数、减数分裂Ⅱ期(MⅡ)卵率、受精率、卵裂率、有效胚胎率、卵母细胞利用率和胚胎利用率等方面的差异。结果在A、B两组患者的年龄[(34.9±4.9)岁vs.(33.3±4.5)岁,P=0.006]、体质量指数(BMI)[(22.5±3.2)kg/m^(2) vs.(21.6±2.6)kg/m^(2),P=0.027]存在一定差异的前提下,A组获卵数与B组相当[(11.2±7.0)vs.(12.9±7.3),P=0.059]。在拮抗剂方案COH周期,两组患者年龄相近(P>0.05),此时两组的获卵数[(13.7±7.1)vs.(14.8±7.6),P=0.340]及其他结局指标均无统计学差异(P>0.05)。将所有患者根据年龄分层分析,高龄(≥35岁)亚组中,A组患者受精率[(78.1±19.6)%vs.(69.1±25.8)%,P=0.039]、卵裂率[(98.9±3.2)%vs.(93.7±22.1)%,P=0.039]和卵母细胞利用率[(44.9±30.6)%vs.(34.1±23.5)%,P=0.037]显著高于B组;低龄(<35岁)亚组中,A、B两组患者各项结局指标均无统计学差异(P>0.05)。通过逐步多元回归分析,确定COH方案和年龄是获卵数的预测因素(P<0.001),最终回归模型可解释28.8%的反应变异性。结论芳乐舒与Puregon两种rFSH具有相似的获卵数和获胚结局,在高龄人群中芳乐舒诱导的卵母细胞质量可能较高。

经后增殖方含药血清对超排卵大鼠卵巢颗粒细胞GDF9表达及凋亡的调控机制

【目的】观察益气血法经后增殖方含药血清对超排卵大鼠卵巢颗粒细胞生长分化因子9(GDF9)表达及凋亡的调控机制。【方法】制备超排卵大鼠血清(空白血清)和经后增殖方灌胃的超排卵大鼠血清(含药血清)。建立控制性超排卵(COH)大鼠模型,收集卵巢颗粒细胞。实验分为5组:空白血清组,含药血清组,含药血清+SB203580[p38丝裂原活化蛋白激酶(p38MAPK)抑制剂]组,含药血清+PDTC[核转录因子κB(NF-κB)抑制剂]组,含药血清+SB203580+PDTC组。采用实时定量聚合酶链反应(qRT-PCR)法检测p38MAPK、酪蛋白激酶2(CK2)、核转录因子κB抑制因子α(IκBα)、NF-κB、GDF9 mRNA表达水平,蛋白免疫印迹(Western Blot)法检测GDF9蛋白表达水平,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测卵巢颗粒细胞凋亡。【结果】经后增殖方含药血清降低COH大鼠卵巢颗粒细胞的p38MAPK和NF-κB mRNA表达,升高CK2和IκBαmRNA表达,提高GDF9 mRNA和蛋白的表达水平,降低卵巢颗粒细胞的凋亡率。单独添加p38MAPK抑制剂SB203580与单独添加NF-κB抑制剂PDTC均能促进GDF9 mRNA和蛋白表达、降低卵巢颗粒细胞凋亡率。【结论】益气血法经后增殖方含药血清可促进超排卵大鼠卵巢颗粒细胞GDF9表达,抑制卵巢颗粒细胞凋亡,其机制可能与调控p38MAPK和NF-κB双信号通路基因表达有关。

Pharmacogenetic study of Asn680Ser and-29A>G in FSHR gene in Chinese women undergoing controlled ovarian hyperstimulation

The outcome of controlled ovarian hyperstimulation(COH)is various and unpredictable.According to previous studies,2 single nucleotide polymorphisms,Asn680Ser and-29A/G,have a pharmacogenetic association with ovarian response to COH.However,studies on the Asn680Ser polymorphism have yielded inconsistent conclusions and only a few studies with small sample sizes have been performed on-29A/G.The association of these 2 polymorphisms with ovarian response remains unclear.The present study evaluated the association of Asn680Ser and-29A/G genotypes with COH.A total of 414 Chinese women undergoing in vitro fertilization-embryo transfer were included.Genotypes for these single nucleotide polymorphisms were identified by high-resolution melting-curve analysis.The value of exogenous follicle-stimulating hormone dosage per oocyte divided by the body surface area(Dosage/Oocyte
Surface)was calculated for each patient as an indicator of ovarian response.The results of statistical analyses showed no association between Asn680Ser genotype and ovarian response.As for-29A/G,heterozygote individuals had more oocytes retrieved(P=0.034).Combinatorial analysis of these 2 single nucleotide polymorphisms showed that genotype A/G-Asn/Asn had lower basal-follicle-stimulating hormone and more oocytes retrieved.Analysis of genotype association with ovarian response also revealed this genotype had a significantly higher risk of developing hyper response(OR=7.86;95%CI:1.31-9.43).To some extent,there were associations between the studied polymorphisms and ovarian response;however,the power of this link is weak and has limited value for clinical prediction.

IVF促排卵过程中GnRH拮抗剂添加日LH水平对助孕结局的影响

目的 探索体外受精-胚胎移植技术(IVF-ET)助孕过程中促性腺激素释放激素(GnRH)拮抗剂添加日血黄体生成素(LH)水平对妊娠结局和胚胎质量的影响。方法 回顾性分析2018年1月至2022年12月于武汉大学中南医院生殖医学中心接受拮抗剂方案常规IVF-ET治疗且预期卵巢正常反应的女性不孕症患者资料,根据其拮抗剂添加日LH水平进行分组,比较各组临床妊娠率、着床率、卵子成熟度、受精率、卵裂率、2原核胚胎比率、D3优质胚胎率、囊胚形成率,并绘制受试者工作特征(ROC)曲线评估LH水平对临床妊娠的预测价值。结果 研究共纳入188例患者,其拮抗剂添加日LH水平的中位值为3.79(2.48,6.14)mIU/mL。当LH <2.48 mIU/mL时鲜胚移植的临床妊娠率和着床率均最低(P <0.05),而LH> 6.14 mIU/mL时则具有最高的临床妊娠率和着床率(P <0.01),但各组之间的配子和胚胎发育参数差异无统计学意义(P>0.05)。ROC曲线下面积为0.678,LH水平对预测临床妊娠具有一定的准确性。结论 控制性超促排卵过程中LH水平高于6.14 mIU/mL时使用拮抗剂可获得最优的临床妊娠结局。

卵巢过度刺激综合征危险因素和预测模型的研究进展

卵巢过度刺激综合征是控制性卵巢刺激过程中的常见并发症,不仅对胚胎移植策略产生影响,严重时甚至威胁患者的生命健康。目前已有越来越多的研究探讨卵巢过度刺激综合征的危险因素和生物标志物,并构建了一系列风险预测模型。本文对近年来卵巢过度刺激综合征的危险因素和风险预测模型的研究进展进行综述,以期为临床早期识别高危人群、及时制定有效预防措施提供依据,并为模型的选择和改良提供参考。

卵泡期与黄体期长方案鲜胚移植周期活产率和累积活产率比较

目的比较卵泡期长方案与黄体期长效长方案促排卵后鲜胚移植周期的活产率和每取卵周期累积活产率,探讨两种垂体降调节方案的优劣势。方法回顾性分析2018年1月至2021年12月间于宁波大学附属妇女儿童医院生殖中心行体外受精-胚胎移植(IVF-ET)治疗、采用卵泡期长方案或黄体期长效长方案促排、卵巢储备功能正常患者的临床资料(共1969个周期),并根据促排卵方案不同分为卵泡期组(使用卵泡期长方案促排卵,461个周期)和黄体期组(使用黄体期长效长方案促排卵,1508个周期)。比较两组患者的一般情况及临床结局。结果两组患者的女性年龄、不孕年限、体质量指数(BMI)、抗苗勒管激素(AMH)水平、不孕原因等一般资料比较均无显著性差异(P>0.05)。卵泡期组的Gn天数显著高于黄体期组[(11.0±3.3)d vs.(10.6±3.1)d](P<0.01),Gn总剂量显著低于黄体期组[(2390.9±331.3)U vs.[(2645.5±308.1)U](P<0.01)。两组患者的优势卵泡数、获卵数及可利用胚胎数比较均无显著性差异(P>0.05)。卵泡期组HCG日E 2、LH及P水平均显著低于黄体期组(P<0.01)。两组患者的移植日内膜厚度、移植胚胎数比较均无显著性差异(P>0.05)。卵泡期组鲜胚移植周期活产率略低于黄体期组(44.81%vs.49.34%),差异尚无统计学意义(P=0.26)。卵泡期组的中重度卵巢过度刺激综合征(OHSS)发生率(0.87%vs.1.59%)及每取卵周期累计活产率(68.11%vs.70.76%)均略低于黄体期组,但差异尚无统计学意义(P>0.05)。结论对于卵巢储备功能正常的女性,使用卵泡期长方案促排卵可获得与黄体期长方案相似的临床结局。

补肾调经方对控制性超促排卵小鼠甲状腺功能和卵巢储备的影响

目的:观察补肾调经方对控制性超促排卵(controlled ovarian hyperstimulation,COH)小鼠甲状腺功能及卵巢储备的影响。方法:8~10周龄ICR系雌性小鼠随机分为正常组、COH组和补肾组,每组20只。COH组和补肾组采用由促性腺激素释放激素激动剂(GnRH-a)、人绝经期促性腺激素(HMG)和人绒毛膜促性腺激素(hCG)组成的COH方案,补肾组在给予以上方案的同时灌胃补肾调经方。放射免疫法(RIA)检测血清四碘甲腺原氨酸(T_(4))、促甲状腺激素(TSH)、雌二醇(E_(2))和孕酮(P)水平;ELISA检测血清抗缪勒氏管激素(AMH)水平;HE染色计数卵巢组织切片不同阶段卵泡。结果:与正常组相比,COH组小鼠血清T_(4)、AMH、E_(2)和P水平降低(P<0.05),TSH水平升高(P<0.05),黄体数增加,初级卵泡和次级卵泡数减少(P<0.05);与COH组相比,补肾组小鼠血清T_(4)和AMH水平升高(P<0.05),TSH浓度降低(P<0.05),黄体数减少,初级卵泡和次级卵泡数增加(P<0.05)。结论:COH可能导致小鼠甲状腺功能障碍并降低卵巢储备,补肾调经方对改善COH小鼠甲状腺功能和卵巢储备发挥一定作用。

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.