IVF超促排卵过程中对卵巢反应性的预测

不孕患者在控制性超促排卵过程中卵巢的反应是影响体外受精-胚胎移植结局的关键之一。在进行超促排卵前正确预测卵巢的反应有助于选择合理的治疗方案,调整用药剂量,提高成功率。为此,临床上采用了众多的反映卵巢功能的指标,包括卵泡刺激素、雌激素、抑制素及B超等,但是临床上对这些指标的预测价值看法不一。     

罗格列酮用于多囊卵巢综合征患者促排卵周期的疗效观察

目的：探讨罗格列酮对多囊卵巢综合征有胰岛素抵抗(IR)患者促排卵治疗的效果。方法：将2001年6月至2002年6月81例患者随机分为A、B、C三组，分别给予促排卵药、罗格列酮、罗格列酮与促排卵药合用，比较三组用药前后胰岛素抵抗指数(Homa IR)、游离脂肪酸(FFA)、肿瘤坏死因子(TNFα)和排卵率的变化。结果：罗格列酮治疗前后患者Homa IR指数、血清FFA和TNFα明显下降(P＜0．05)。C组排印卑明显化于A组(P＜0．05)和B组(P＜0．005)。结论：罗格列酮能有效地改善胰岛素抵抗，提高排卵率。     

多囊卵巢综合征和胰岛素相关的卵巢功能调节系统

多囊卵巢综合征(PCOS)，是不排卵性不孕的最常见原因，目前其发病机制尚不清楚，但越来越多的研究表明胰岛素相关的卵巢功能调节系统(insulin-related ovarian regulatory system)在PCOS的发生发展过程中起重要作用，这一发现对于PCOS患者的l临床治疗亦有重大指导意义。从胰岛素相关的卵巢功能调节系统成员参与PCOS发病的可能环节及对临床治疗的指导意义等综述。     

超排卵对卵巢功能的影响

超排卵（superovulation）是指用促排卵药物促使多个卵泡发育并成熟，又称为控制性超排卵（controlled ovarian hyperstimulation，COH），是治疗女性不孕症的一种重要手段。自1960年以来，促排卵药物广泛应用在各种不孕症患者的治疗中，而且随着近年不孕症发病率的增高和辅助生育技术普及其应用日益增多。超排卵通常用于排卵障碍以及辅助生育技术（AID、IVF等）的促排卵周期，目的是通过增加获取的成熟卵子的数目，提高妊娠率。由于超排卵药物毕竟使卵巢处于非生理状态的刺激下，所以超排卵技术对卵巢功能的影响始终受到关注，本文就与超排卵有关的几个主要问题综述如下。     

微刺激促排卵方案在PCOS患者IVF中的应用

目的:探讨微刺激促排卵方案在多囊卵巢综合征(PCOS)患者IVF中的应用。方法:将行IVF-ET的不孕患者分为3组:PCOS长方案组(A组,n=31)、PCOS微刺激组(B组,n=23)和非PCOS长方案对照组(C组,n=25)。比较3组的年龄、不孕年限、基础内分泌、口服避孕药后基础内分泌及IVF结局。结果:①年龄、不孕年限、基础FSH(bFSH)组间比较均无统计学差异(P>0.05);bLH、bLH/bFSH、bT在A组和B组中均明显高于C组(P<0.05);用口服避孕药后A组和B组LH、LH/FSH、T明显降低,使3组间内分泌比较无统计学差异(P>0.05)。②A组的受精率、卵裂率低于C组(P<0.05);Gn使用天数、获卵数、可利用胚胎数、优质胚胎数高于C组(P<0.05);Gn使用总量、种植率、临床妊娠率、流产率A、C组间比较均无统计学差异(P>0.05)。③B组受精率、卵裂率低于C组(P<0.05);Gn使用总量及Gn使用天数比C组明显减少(P<0.05);获卵数、可用胚胎数、优质胚胎数高于C组(P<0.05);B、C组间种植率、临床妊娠率、流产率比较无统计学差异(P>0.05)。④B组Gn使用总量及Gn使用天数比A组明显减少(P<0.05);B组获卵数、受精率、卵裂率、优质胚胎数、可利用胚胎数等指标与A组比较均无统计学差异(P>0.05)。⑤B组hCG注射日E2水平及移植日子宫内膜厚度明显低于A组(P<0.05),但种植率、临床妊娠率、流产率等方面与A组比较均无统计学差异(P>0.05)。结论:①口服避孕药在调整PCOS患者内分泌,降低PCOS患者LH、T方面有较好的作用,能改善PCOS患者内分泌环境;②PCOS患者行IVF时采用克罗米酚(CC)加hMG微刺激可降低hCG注射日E2水平,减少OHSS的发生。③CC加hMG微刺激方案对PCOS患者行IVF促排卵可能是相对经济、有效、安全的方法。     

多囊卵巢综合征患者初次IVF/ICSI-ET助孕临床方案选择

目的:探讨多囊卵巢综合征(PCOS)患者初次进行体外受精/卵胞质内单精子注射-胚胎移植(IVF/ICSI-ET)助孕时最佳方案的选择。方法:≤45岁初次行IVF/ICSI-ET助孕的PCOS患者1 407名,按照超长方案(A组)、长方案(B组)、短方案(C组)和拮抗剂方案(D组)分成4组,比较各组患者基本临床特征、控制性超促排卵(COH)特征、重度卵巢过度刺激综合征(OHSS)发生率及临床结局。结果:除A组年龄偏大外,各组体质量指数(BMI)、基础血清性激素水平相当;A组与B组促性腺激素(Gn)使用天数、剂量高于C组和D组,C组与D组h CG注射日血清LH、E2水平明显高于A组和B组,h CG注射日内膜厚度A组与B组明显高于C组和D组,A组临床妊娠率、持续妊娠率和活产率明显高于其他各组(P0.05)。重度OHSS、异位妊娠率、早期流产率各组间无统计学差异(P0.05)。多元因素回归显示IVF方案(OR=0.813,95%CI=0.667~0.991)、h CG注射日内膜厚度(OR=1.262,95%CI=1.148~1.388)和空腹血糖水平(OR=1.395,95%CI=1.021~1.905)可能影响PCOS患者临床妊娠率(P0.05)。结论:PCOS患者在初次尝试IVF助孕时,选择超长方案可获得更佳的子宫内膜容受性,提高临床妊娠率、持续妊娠率以及活产率,且不增加重度OHSS发生率。不足之处是Gn应用时间较长、剂量较大,可能增加临床治疗费用。     

多囊卵巢综合征和胰岛素相关的卵巢功能调节系统

多囊卵巢综合征(PCOS),是不排卵性不孕的最常见原因,目前其发病机制尚不清楚,但越来越多的研究表明胰岛素相关的卵巢功能调节系统(insulin-related ovarian regulatory system)在PCOS的发生发展过程中起重要作用,这一发现对于PCOS患者的临床治疗亦有重大指导意义.从胰岛素相关的卵巢功能调节系统成员参与PCOS发病的可能环节及对临床治疗的指导意义等综述.     

IVF过程中延长HCG暴露时间对PCOS患者临床结局的影响

目的:探讨多囊卵巢综合征(PCOS)患者IVF/ICSI-ET过程中延长HCG暴露对IVF临床结局的影响。方法:回顾分析2015年10月～2017年10月于我院生殖医学中心行体外受精/胞浆内单精子注射-胚胎移植(IVF/ICSI-ET)的PCOS患者199例,共199个周期,根据HCG暴露时间分为两组:35～36h组(对照组,78例)和37～38h组(实验组,121例)。比较两组患者的基本情况、获卵、受精、胚胎情况及临床妊娠等。结果:两组患者的一般情况、IVF过程中的Gn天数、Gn量、激素水平、移植日内膜厚度均无统计学差异(P0.05)。两组的卵泡穿刺数无统计学差异,实验组的获卵数、MII卵数、2PN受精数及临床妊娠率均高于对照组,且有统计学差异(P0.05)。实验组的活产率高于对照组,但无统计学差异(P0.05)。结论:适当延长PCOS患者的HCG暴露时间,可促使卵母细胞复合物与卵泡壁充分分离,增加获卵数,促进卵子最终成熟、核质同步化,改善卵子及胚胎质量,进一步提高临床妊娠率。     

多囊卵巢综合征促排卵方案的现状

多囊卵巢综合征(PCOS)患者最常表现闭经或月经稀发,无排卵和不孕。生育年龄有生育要求的治疗以促排卵、调节代谢为主。PCOS促排卵的结局易造成多卵泡发育,卵巢过度刺激综合征(OHSS)、多胎妊娠的发生率较高,或者对促排卵药物不反应或卵泡期过长,提早黄素化等。目前应用于临床的促排卵药物及促排卵方案较多。本文将针对目前PCOS的促排方案加以综述和比较。     

FOXL2对IVF周期卵巢反应性的影响

目的:探讨FOXL2在人卵巢黄素化颗粒细胞表达与IVF周期超促排卵过程中卵巢反应性的关系。方法:采用半定量逆转录聚合酶链反应(RT-PCR)技术测定84例体外受精-胚胎移植(IVF-ET)周期中卵巢黄素化颗粒细胞FOXL2 mRNA的表达。结果:卵巢低反应型(卵泡数≤3个)FOXL2 mRNA表达量显著低于中反应型(卵泡数4~13个)和高反应型(卵泡数≥14个)(P<0.05);FOXL2表达强度与血清基础FSH呈负相关(r=-0.46,P<0.05)。结论:卵巢颗粒细胞上FOXL2水平影响体外受精-胚胎移植过程中卵巢对促性腺激素的反应。卵巢颗粒细胞上FOXL2表达水平与卵巢储备功能有关,卵巢功能下降可能与卵巢颗粒细胞上FOXL2表达水平降低有关。     

Basal serum testosterone levels correlate with ovarian response but do not predict pregnancy outcome in non-PCOS women undergoing IVF

Purpose

To evaluate basal testosterone (T) levels in women undergoing in vitro fertilization (IVF) cycles and examine the association between basal T levels and ovarian response or IVF pregnancy outcome.

Methods

We retrospectively analyzed 1413 infertile Chinese women undergoing their first IVF treatment at our institution’s reproductive center from March 2011 to May 2013. The basal testosterone (T) levels in women undergoing in vitro fertilization (IVF) and the relationship between basal T levels and ovarian response or IVF pregnancy outcome were determined. These patients did not have polycystic ovary syndrome (PCOS) or endometriosis, and were treated with a long luteal down-regulation protocol. Subjects were divided into 2 groups according to basal testosterone (T) levels: Group 1, basal T values <20 ng/dl (n = 473), and Group 2, basal T values >20 ng/dl (n = 940). We evaluated the association of basal T levels with ovarian response and IVF outcome in the two groups.

Results

In this study, BMI, basal follicle-stimulating hormone (FSH) levels, basal luteinizing hormone (LH) levels, antral follicle count (AFC), days of stimulation, total gonadotrophin dose, basal FSH/LH ratio, and the number of follicles >14 mm were significantly different (P < 0.05) between the two groups. Basal T level positively correlated with ovarian reserve function, number of follicles >14 mm on human chorionic gonadotrophin (HCG) day, and total gonadotropin dose. However, basal T levels play no role in predicting IVF pregnancy outcome.

Conclusion

Basal T level can be used as a good predictor for ovarian response and the number of large follicles on HCG day. Additionally, we may use basal T level as a marker to predict FSH dosage. In general women, lower level of T might relate with potential poor ovarian response. However, based on our data, basal T levels do not predict pregnancy outcome.     

Basal serum testosterone levels correlate with ovarian reserve and ovarian response in cycling women undergoing in vitro fertilization

This study aimed to investigate the association between basal serum testosterone levels and in vitro fertilization (IVF) parameters in cycling women. A retrospective cohort study was performed at a clinical IVF center, and 495 women with regular menstruation were enrolled. Serum testosterone levels were measured before the start of IVF treatment cycle. We found that basal serum testosterone levels were negatively associated with female age and FSH/LH ratios. In contrast, we found a positive correlation between serum testosterone levels and the number of oocytes and available embryos. However, there was no significant association between testosterone levels and pregnancy outcome. Our results suggest that basal serum testosterone levels were significantly?related to certain?classic?indicators of ovarian?reserve, such as age and FSH/LH ratios. Increased testosterone levels improved ovarian response in cycling women, but they fail to predict pregnancy and miscarriage rate.     

Low testosterone levels in women with diminished ovarian reserve impair embryo implantation rate: a retrospective case-control study

Objective

To investigate the association of basal testosterone (T) levels with the outcome of in vitro fertilization (IVF) in women with diminished ovarian reserve (DOR).

Methods

Complete clinical data on the first 223 IVF cycles in women with DOR were retrospectively analyzed. The associations of basal follicle stimulating hormone, luteinizing hormone, estradiol, and T levels with ovarian response and IVF outcome were studied.

Results

Basal T levels were significantly different between pregnant and non-pregnant women. However, basal T levels showed no correlation with controlled ovarian hyperstimulation parameters after adjusting for age. The association of basal T levels with pregnancy rate was significant after adjusting for other impact factors. Using receiver operating characteristic (ROC) analysis, the basal T level of 1.115 nmol/L for predicting pregnancy outcome had a sensitivity of 82.80 % and specificity of 58.09 %. The women were divided into two groups based on this value; although the clinical characteristics and ovarian stimulation parameters were similar, the clinical pregnancy (16.18 % (11/68) vs. 40.15 % (53/132), respectively, p = 0.000) and implantation rates (10.07 % (15/149) vs. 22.41 % (65/290), respectively, p = 0.002) were significantly different in the low and high T level groups.

Conclusion

In women with DOR, the basal T level presented a positive association with pregnancy outcome in IVF. The poor reproductive outcome observed in women with lower basal T levels may be due to the decreased implantation rate.     

Serum anti-Mullerian hormone levels correlate with ovarian response in idiopathic hypogonadotropic hypogonadism

Purpose

The role of serum AMH levels in prediction of ovarian response in idiopathic hypogonadotropic hypogonadism (IHH) was evaluated.

Material method(s)

Twelve patients with IHH underwent controlled ovarian hyperstimulation (COH) for IVF were enrolled in this prospective study. Serum AMH levels were studied on the 2nd or 3rd day of an induced menstrual cycle by a preceding low-dose oral contraceptive pill treatment. A fixed dose (150–300 IU/day) of hMG was given in all COH cycles. Correlations between serum AMH levels, COH outcomes and embryological data were investigated.

Results

Mean serum AMH levels was 3.47 ± 2.15 ng/mL and mean serum peak estradiol was 2196 ± 1705 pg/mL. Mean number of follicles >14 mm, >17 mm on hCG day and MII oocytes were 4.14 ± 3.2, 4 ± 2.5 and 7.28 ± 3.5, respectively. Mean number of grade A embryos and transferred embryos were 3.28 ± 2.4 and 2.5 ± 0.7, respectively. The clinical pregnancy rate per patient was 41.6 % (5/12). Positive correlations were observed between serum AMH levels and MII oocytes (r = 0.84), grade A embryos (r = 0.85), serum peak estradiol levels (r = 0.87), and number of follicles >14 mm (r = 0.83) and >17 mm (r = 0.81) on hCG day, respectively.

Conclusion

AMH appears as a promising marker of ovarian response in patients with IHH undergoing IVF.     

基础雄激素及卵泡液雄激素水平与卵巢反应性及妊娠结局关系的探讨

目的:探讨基础雄激素及卵泡液雄激素水平与卵巢反应性及妊娠结局的关系。方法:选取行IVF/ICSI助孕治疗的130例不孕症女性,将研究对象分为卵巢储备功能低下组、卵巢储备功能正常组。ELISA法检测基础雄激素及卵泡液中睾酮浓度。结果:卵巢储备功能低下组中,卵巢低反应组与正常反应组的基础雄激素水平比较,差异有统计学意义(P=0.037);两组卵泡液中雄激素水平比较,差异无统计学意义(P=0.475)。卵巢储备功能正常组中,卵巢低反应组与正常反应组的基础雄激素水平及卵泡液雄激素水平比较,差异均无统计学意义(P=0.426,P=0.594)。20例进行新鲜周期移植的卵巢储备功能低下患者中,未妊娠组与妊娠组基础雄激素水平及卵泡液中雄激素水平比较,差异均无统计学意义(P=0.400,P=0.656)。89例进行新鲜周期移植的卵巢储备功能正常患者中,未妊娠组与妊娠组的基础雄激素水平及卵泡液中雄激素水平比较,差异均无统计学意义(P=0.380,P=0.930)。结论:卵巢储备功能低下患者,基础雄激素水平与卵巢反应性相关,而与妊娠结局无关;卵泡液中雄激素水平与卵巢反应性和妊娠结局无关。卵巢储备功能正常患者,基础雄激素和卵泡液中雄激素均与卵巢反应性及妊娠结局无关。     

Ovarian response to controlled ovarian hyperstimulation in women with cancer is as expected according to an age-specific nomogram

Purpose

To evaluate the ovarian response to controlled ovarian hyperstimulation (COH) in cancer patients according to an age-specific nomogram for the number of retrieved oocytes.

Methods

Retrospective observational study carried out in a University affiliated fertility clinic. Forty-eight patients with cancer underwent ovarian stimulation for oocyte cryopreservation. An age - specific nomogram for the number of retrieved oocytes was built with 1536 IVF cycles due to male factor exclusively, oocyte donation and age related fertility preservation. The number of oocytes retrieved in cancer patients was compared to the expected response according to the nomogram using the Z-score.

Results

The mean number of total retrieved oocytes in patients with cancer was 14.04 ± 8.83. After applying the Z-score to compare the number of retrieved oocytes between women with cancer and the expected response according to the age-specific nomogram, we did not observe a statistically significant difference (Z-score 0.23; 95 % CI [−0.13-0.60]).

Conclusion(s)

According to our results, patients with cancer exhibit an ovarian response as expected by age. Despite the limitation of the sample size, the obtained results should encourage oncologists for early referral of women with cancer to fertility specialists.     

基础FSH/LH比值对预测年轻不孕患者IVF-ET周期卵巢反应性的影响

目的:探讨基础FSH和LH比值预测基础FSH水平正常且年轻不孕患者卵巢反应性的临床价值。方法:回顾分析2004年6月至2005年5月因男方因素或输卵管因素行体外受精-胚胎移植(in-vitrofertilization-embryotransfer,IVF-ET)治疗的年轻(年龄≤35岁)且基础FSH水平正常(≤8.5IU/L)不孕患者237例的临床资料,共计237个治疗周期,依据FSH/LH不同比例分为3组,A组(n=44)FSH/LH<1;B组(n=143)FSH/LH12;C组(n=50)FSH/LH>2。比较各组间的年龄、激素水平、卵巢反应、IVF的实验室结果以及妊娠情况。结果:3组患者的年龄、窦卵泡数、基础E2值、受精率、卵裂率和妊娠率两两相比无统计学差异(P>0.05),但A、B两组间的基础FSH值、基础LH值、E2峰值和成熟卵泡数差异有统计学意义(P<0.05);A、C两组间基础FSH值、基础LH值、E2峰值、促性腺激素(gonadotropin,Gn)总用量、Gn平均每日用量、Gn用药时间及获卵数和成熟卵泡数的差异有统计学意义(P<0.05);B、C两组间基础LH值、E2峰值、促性腺激素总用量、Gn平均每日用量和Gn用药时间比较也有明显差异(P<0.05)。结论:FSH正常的年轻妇女,FSH/LH>2的卵巢反应性明显低于FSH/LH<1者;FSH/LH比值是预测基础FSH正常且年轻不孕者卵巢反应性的一项较好指标。