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.

COH过程中雌二醇下降对拮抗剂方案IVF-ET助孕结局的影响

目的分析拮抗剂方案控制性促排卵(COH)过程中雌二醇(E_(2))水平下降对体外受精/卵胞浆内单精子注射-胚胎移植(IVF/ICSI-ET)助孕结局的影响。方法回顾性分析2019年1月至2022年12月于我院生殖医学科行IVF/ICSI-ET时采用拮抗剂方案促排卵的385个周期的临床资料,根据患者促排卵过程中E_(2)水平的变化情况分为3组:扳机日前E_(2)下降者为A组(n=38)、扳机日E_(2)下降者为B组(n=81),促性腺激素(Gn)使用过程中E_(2)持续上升者为C组(n=266),比较各组患者的一般情况及IVF-ET结局。结果各组患者间年龄、抗苗勒管激素(AMH)、基础窦卵泡计数(AFC)及基础性激素水平等一般资料比较均无显著性差异(P>0.05)。A组和B组扳机日E_(2)水平、孕酮水平、LH水平、E_(2)/≥14 mm卵泡数、获卵数及扳机日E_(2)/获卵数均显著低于C组(P<0.05);A组的Gn使用天数显著多于B组和C组,而Gn启动剂量显著低于B组和C组(P<0.05);A组和B组的MⅡ卵数、2PN受精数、优质胚胎数均略低于C组,但尚无显著性差异(P>0.05);各组患者新鲜胚胎移植后的胚胎种植率、临床妊娠率比较亦无显著性差异(P>0.05)。结论采用拮抗剂方案促排卵过程中,E_(2)的下降可能会影响扳机日的E_(2)、孕酮、LH水平及获卵数,但对胚胎质量和新鲜胚胎移植结局可能无显著影响。

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.

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。

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。

121个染色体平衡易位携带者PGD周期COH的卵巢反应性分析

目的:探讨常染色体平衡易位对女性携带者控制性超促排卵(COH)中卵巢反应性的影响。方法:回顾分析于我院行胚胎植入前遗传学诊断(PGD)的109对常染色体平衡易位夫妇,共121个周期,其中夫妇中仅女方为平衡易位携带者56例(63个周期,研究组),包括罗伯逊易位携带者23例(27个周期),相互易位携带者33例(36个周期);夫妇中仅男方为平衡易位携带者53例(58个周期,对照组),包括罗伯逊易位携带者30例(32个周期),相互易位携带者23例(26个周期)。分析COH过程中,研究组和对照组的女方卵巢反应性指标和妊娠结局。结果:两组的女方年龄、体重指数(BMI)、基础内分泌及窦卵泡数(AFC)均无显著差异(P>0.05)。两组的卵巢反应性指标,包括Gn总量、HCG注射日E2水平、获卵数、D3胚胎数、可移植胚胎数及移植胚胎数,以及移植周期临床妊娠率、早期流产率及种植率均无显著差异(P>0.05)。单独就罗伯逊易位携带者或相互易位携带者而言,两组的各指标均无显著差异。排除可能影响COH卵巢反应性的女方因素,研究组与对照组的各指标均无显著差异。结论:染色体平衡易位,包括罗伯逊易位或相互易位并不影响COH中的卵巢反应性。应将染色体平衡易位女性携带者视为正常卵巢反应性,采用合适剂量的促性腺激素进行控制性促排卵。

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。

长效GnRH-a长方案在年轻患者COH中应用优势的探讨

目的:通过比较促性腺激素释放激素(GnRH-a)长效长方案和短效长方案在控制性超排卵(COH)中应用的效果,探讨长效GnRH-a长方案在年轻患者体外受精-胚胎移植(IVF-ET)中应用的优势。方法:回顾性分析GnRH-a长效长方案(1045个周期)和GnRH-a短效长方案(555个周期)在年轻患者COH中应用的资料,按长方案降调节中使用长效或短效GnRH-a分为两组,观察比较两组超排卵效果及助孕结局。结果:在年轻患者中长效长方案组的促性腺激素(Gn)用量明显减少、超排时间延长、周期取消率升高,hCG日LH水平明显低于短效长方案组,获卵数、可移植胚胎数均明显多于短效长方案组,冷冻率明显高于短效长方案组,差异均有统计学意义(P<0.05),两组临床妊娠率比较无明显差异(P>0.05)。结论:对于年轻、卵巢储备正常的患者人群,长效长方案不失为控制性超排卵方案的一种好选择。

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。

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.

反复控制性超促排卵对胚胎发育及妊娠结局的影响

目的探讨反复控制性超促排卵(COH)对胚胎发育潜能及妊娠结局的影响。方法回顾性分析2014年1月至2020年7月于河南省人民医院生殖医学中心接受体外受精-胚胎移植(IVF-ET)助孕治疗的7086例患者的临床资料,根据COH次数将患者分为A组(首次行COH者)、B组(第2次行COH者)、C组(第3次或第4次行COH者),比较3组患者的胚胎发育指标(卵子成熟率、正常受精率、正常卵裂率、可利用胚胎率)和妊娠结局(胚胎种植率、生化妊娠率、临床妊娠率、异位妊娠率、流产率、早期流产率)。结果3组患者的卵子成熟率、正常受精率随COH次数的增加有下降趋势,但差异无统计学意义(P>0.05)。A组患者的正常卵裂率和可利用胚胎率均高于B组和C组(P<0.05);B组与C组患者的正常卵裂率、可利用胚胎率比较差异无统计学意义(P>0.05)。A组患者的胚胎种植率、生化妊娠率、临床妊娠率均显著高于B组和C组(P<0.05);B组与C组患者的胚胎种植率、生化妊娠率、临床妊娠率比较差异无统计学意义(P>0.05)。3组患者异位妊娠率比较差异无统计学意义(P>0.05)。B组患者的流产率和早期流产率高于A组(P<0.05);其余各组患者的流产率和早期流产率比较差异均无统计学意义(P>0.05)。结论反复COH可能会在一定程度上降低IVF-ET周期患者的正常卵裂率、可利用胚胎率、胚胎种植率、生化妊娠率、临床妊娠率及流产率。

卵泡输出率与血清let-7g、let-7f联合评估超促排卵卵巢反应及临床意义

目的:研究卵泡输出率(FORT)与血清let-7g、let-7f联合评估超促排卵患者卵巢反应价值及临床意义。方法:收集本院2020年1月-2021年12月行体外受精-胚胎移植术(IVF-ET)患者97例临床资料,根据患者获卵数分为卵巢低反应组、中反应组及高反应组,比较3组FORT、血清let-7g、let-7f水平,分析不同妊娠结局及FROT水平患者临床特征、促排卵效果、实验室指标及治疗结局,分析FORT、血清let-7g及let-7f评估患者卵巢反应性价值。结果:血清let-7g、let-7f水平卵巢中反应组高于低反应组及高反应组(P<0.05),低反应组与高反应组无差异(P>0.05);FORT水平在低反应组、中反应组及高反应组依次升高(P<0.05)。妊娠组血清let-7g、let-7f、FORT、获卵数、受精率及优质胚胎率均高于非妊娠组(P<0.05);低FROT组AFC数低于中FROT组及高FROT组(P<0.05),低FROT组、中FROT组及高FROT组获卵数、受精率、优质胚胎率及临床妊娠率依次升高(P<0.05)。患者血清let-7g与let-7f水平呈正相关,两者与TORF无明显相关性。FORT、血清let-7g及let-7f单独应用时,预测卵巢低反应性或高反应性的价值均以let-7f最高(AUC=0.754、0.767),其次是FORT(AUC=0.750、0.734),3项指标联合应用(AUC=0.859、0.848)提高了评估效能。结论:FORT及血清let-7g、let-7f miRNA表达在反映卵巢反应性中均具一定效能,可作为指导控制性超排卵方案制定的潜在指标。