Ultrasonographical predictive factors of ovarian response to stimulation prior to in vitro fertilization

OBJECTIVE: Evaluate whether ovarian antral follicles number, ovarian volume and ovarian area are predictive of ovarian response. PATIENTS AND METHODS: Prospective cohort analysis of 41 women with normal basal serum FSH concentration, who were undergoing their IVF cycle. The ovarian antral follicle number, the ovarian volume and area were determined by transvaginal ultrasonography on the third menstrual day for 20 women, and after pituitary suppression for 21 women. The main outcome measures are the number of follicles the day of HCG with a diameter >or=14 mm, the number of oocytes retrieved and the number of embryos. RESULTS: The antral follicle count was significantly correlated to the number of follicles (R=0.7; P<0.001), to the number of oocytes retrieved (R=0.46; P=0.008) and to the number of embryos (R=0.44; P=0.01). The ovarian volume and area was significantly correlated to the number of follicles. DISCUSSION AND CONCLUSION: The total antral follicle number on day 3 has a predictive value for favourable IVF outcome. Because this sonographic count is easy, safe and inexpensive it should be performed prior every IVF cycle.     

Three-dimensional ultrasonographic ovarian measurements and in vitro fertilization outcome are related to age

OBJECTIVE: To evaluate whether the number of ovarian antral follicles, ovarian volume, and ovarian stromal blood flow change with age and to prospectively analyze whether three-dimensional ultrasonographic measurements predict ovarian response and IVF outcome. DESIGN: Prospective analysis. SETTING: Assisted reproductive unit. PATIENT(S): Fifty-six consecutive women 22 to 43 years of age with normal basal serum FSH concentrations who were undergoing their first IVF cycle. MAIN OUTCOME MEASURE(S): Number of ovarian antral follicles, ovarian volume, and ovarian stromal flow index were determined by three-dimensional and power Doppler ultrasonography. Pretreatment measurements were compared with number of recovered oocytes, fertilization rates, and pregnancy rates. RESULT(S): As patient age increased, significant trends in ovarian volume, number of follicles, and stromal vascularity decreased. Three-dimensional ovarian measurements and fertilization rates differed significantly among age groups. For each age group, a higher number of antral follicles, greater ovarian volume, and favorable ovarian stromal vascularity was associated with higher number of retrieved oocytes and increased pregnancy rates. CONCLUSION(S): Increasing patient age is associated with poor ovarian response, as represented by smaller ovarian volume, lower antral follicle count, and poor stromal vascularity. Three-dimensional power Doppler ultrasonography can help to individualize IVF in patients regardless of age.     

Role of ultrasonographic markers of ovarian reserve in prediction of IVF and ICSI outcome

The aim of the study was to assess correlation of ultrasonographic markers of ovarian reserve and IVF/ICSI outcome. Two-hundred twelve IVF/ICSI patients were included. Upon pituitary suppression confirmation, antral follicle count (AFC), ovarian volume (OV), and ovarian stromal indices [vascularization index (VI), flow index (FI), and vascularization flow index (VFI)] were assessed by three-dimensional (3D) and power Doppler (PD) ultrasound and correlated with the number of mature oocytes retrieved. The number of mature oocytes retrieved correlated strongly with AFC (r?=?0.832, p?≤?0.001) and OV (r?=?0.835, p?≤?0.001), but weakly with VI (r?=?0.166, p?=?0.016), FI (r?=?0.151, p?=?0.028), and VFI (r?=?0.14, p?=?0.041). AFC and OV correlate strongly with the number of mature oocytes retrieved in IVF/ICSI cycles, whereas 3D PD indices of the ovarian stromal vascularity have a weak correlation.     

Quantification of ovarian power Doppler signal with three-dimensional ultrasonography to predict response during in vitro fertilization

OBJECTIVE: To evaluate whether power Doppler predicts ovarian response to gonadotrophin stimulation during in vitro fertilization (IVF). METHODS: Forty-five women were divided into low-reserve (n = 12) and normal-reserve (n = 33) ovarian groups, according to antral follicle count. Transvaginal three-dimensional power Doppler ultrasonographic examinations were performed after pituitary downregulation and after gonadotrophin stimulation. The antral follicle count, ovarian volume, vascularization index, flow index, vascularization flow index, and mean gray value were measured and related to the number of oocytes retrieved and the pregnancy rate. RESULTS: The number of oocytes retrieved correlated with the antral follicle count (R =.458, P =.004) and ovarian volume (R =.388, P <.016) but not with vascularization index, flow index, vascularization flow index, or mean gray value after pituitary suppression. There was an increase in vascularization index (P <.017), flow index (P <.001), and vascularization flow index (P <.007) during gonadotrophin stimulation in the normal-ovary group but not in the low-ovarian-reserve group. CONCLUSION: According to our results, quantification of power Doppler signal in the ovaries after pituitary suppression does not provide any additional information to predict the subsequent response to gonadotrophin stimulation during IVF. The increase in ovarian power Doppler signal during gonadotrophin stimulation is related to the antral follicle count observed after pituitary suppression.     

Combining cycle day 7 follicle count with the basal antral follicle count improves the prediction of ovarian response

OBJECTIVE: To analyze the predictive value of cycle day 7 follicle count (CD7-FC) for poor ovarian response during IVF in women down-regulated with a luteal start of GnRH analogue (long protocol). DESIGN: A retrospective analysis. SETTING: University hospital. PATIENT(S): Ninety-one consecutive IVF cycles of 82 subjects. INTERVENTION(S): Basal levels of FSH and E2 were determined in the spontaneous cycle before the IVF cycle. During the IVF cycle, the number of basal and CD7 follicles and CD7 endometrial thickness were determined by ultrasound, and CD7 serum E2 levels were measured. MAIN OUTCOME MEASURE(S): Ovarian response determined according to the number of mature oocytes retrieved. RESULT(S): On receiver operating characteristic analysis, CD7-FC had the highest combination of sensitivity and specificity to detect women with poor ovarian response when compared with the basal ovarian reserve tests. When a combined basal antral FC and CD7-FC evaluation was used with the optimum cutoff values of 6.5 and 7.5, respectively, sensitivity and specificity improved to 85% and 90%, respectively. CONCLUSION(S): Cycle day 7 follicle count during a long IVF protocol is helpful in predicting ovarian response in combination with the antral FC. This combination has high positive and negative predictive values. This may help clinicians and women to cancel cycles earlier and decrease the psychological, financial, and medical burden of a later cancellation.     

Sonographic assessment of ovarian reserve. Its correlation with outcome of in vitro fertilization cycles.

Ovarian reserve is a crucial factor for normal ovarian response and the achievement of pregnancy after in vitro fertilization (IVF). Recently, the study of morphological markers by means of ultrasonographic counting of antral follicles (AFC) has proved useful. The present prospective study included 327 consecutive IVF patients who had a basal ultrasound scan of their ovarian reserve during the early follicular phase and had a first IVF cycle between 1 and 3 months later. We performed 313 ovum pick-ups with a mean of 11.1 +/- 7.9 oocytes retrieved. The pregnancy rate per aspiration was 34.5%. Clear and significant differences were observed between normal and low response with respect to AFC, follicle-stimulating hormone (FSH) level and age. We also found that AFC correlated negatively and significantly with age, FSH and LH, and positively and also significantly with the total number of follicles, estradiol level and the number of oocytes retrieved. Using receiver operating characteristic curves, the cut-off value of AFC for poor response was 7 follicles. The value of AFC for predicting pregnancy was lower, although patients with AFC of 8 or more follicles obtained significantly higher pregnancy rates. We consider that AFC should be included in the study of the infertile patient.     

Correlations between antral follicle count and ultrasonographic ovarian parameters and clinical variables and outcomes in IVF cycles

Aims: To assess the correlation between the antral follicle count (AFC) and other ultrasonographic parameters and clinical variables in in vitro fertilization (IVF) cycles. Methods: Pretreatment ultrasonographic evaluation included AFC (total), large (5–10 mm) and small (2–4 mm) antral follicles, ovarian volume, and ovarian Doppler indices. Data were prospectively uploaded and subsequently analysed in relation to IVF cycle results. Results: The study included 128 women (128 cycles). Analysis of body mass index (BMI) yielded a weak significant correlation with large (5–10?mm) AFC but not with other sonographic variables. AFC was significantly correlated with patient age, ovarian volume, number of retrieved oocytes, total dose of used gonadotropins, peak estradiol, number of top-quality embryos, and number of frozen embryos and marginally correlated with number of aspirated immature oocytes. Lower large (5–10?mm) AFC was the only ovarian parameter associated with oral contraception pretreatment compared to nontreatment, even after adjustment for age and BMI. There was no difference in any of the parameters between short and long IVF cycles. Conclusions: BMI is only weakly correlated with AFC. Pretreatment with oral contraceptives may be associated with lower AFC. Pretreatment with gonadotropin-releasing hormone agonist (long protocol) does not alter the ultrasonographic ovarian parameters.     

Sonographic assessment of ovarian reserve. Its correlation with outcome of in vitro fertilization cycles

Ovarian reserve is a crucial factor for normal ovarian response and the achievement of pregnancy after in vitro fertilization (IVF). Recently, the study of morphological markers by means of ultrasonographic counting of antral follicles (AFC) has proved useful. The present prospective study included 327 consecutive IVF patients who had a basal ultrasound scan of their ovarian reserve during the early follicular phase and had a first IVF cycle between 1 and 3 months later. We performed 313 ovum pick-ups with a mean of 11.1 ± 7.9 oocytes retrieved. The pregnancy rate per aspiration was 34.5%. Clear and significant differences were observed between normal and low response with respect to AFC, follicle-stimulating hormone (FSH) level and age. We also found that AFC correlated negatively and significantly with age, FSH and LH, and positively and also significantly with the total number of follicles, estradiol level and the number of oocytes retrieved. Using receiver operating characteristic curves, the cut-off value of AFC for poor response was 7 follicles. The value of AFC for predicting pregnancy was lower, although patients with AFC of 8 or more follicles obtained significantly higher pregnancy rates. We consider that AFC should be included in the study of the infertile patient.     

卵巢储备功能测定在体外受精(IVF)技术中的临床价值探讨

目的:探讨在体外受精-胚胎移植技术中对超促排卵最具临床价值的卵巢储备功能测定指标。方法:将2003.10-2004.10间,105例接受IVF-ET治疗的不孕患者的年龄、基础FSH值、基础窦卵泡数、卵巢体积和卵巢基质血流测定指标与IVF超排中卵巢的实际反应进行对比并作相关性分析。结果:年龄、FSH与获卵数呈非常显著负相关,与促性腺激素(Gn)注射支数呈显著正相关;窦卵泡数、卵巢体积与获卵数呈非常显著正相关,与Gn注射支数呈非常显著负相关;其中以基础窦卵泡数与卵巢反应关系最为密切。卵巢基质血流与卵巢反应无显著相关。结论:年龄、基础FSH值、阴道超声测量基础窦卵泡数和卵巢体积均能预测超排时卵巢对促性腺激素刺激的反应性,并有简便、经济之优点,其中以窦卵泡计数的预测价值最高,窦卵泡计数不仅可用于卵巢低反应的预测,还可预测卵巢反应过激,而年龄与基础FSH仅在预测卵巢低反应中较为敏感,卵巢基质血流对预测卵巢反应的意义有待进一步探讨。     

Ovarian response in three consecutive in vitro fertilization cycles

OBJECTIVE: This study was designed to assess the ovarian response in the same patient in consecutive IVF cycles. DESIGN: Retrospective study. SETTING: Assisted reproductive unit at a university hospital. PATIENT(S): One hundred ninety women who underwent three consecutive cycles of IVF. INTERVENTION(S): All women used a combination of pituitary desensitization and gonadotropin stimulation protocol and underwent oocyte retrieval. MAIN OUTCOME MEASURE(S): Number of follicles produced and number of oocytes retrieved. RESULT(S): There were no significant differences in the number of follicles produced, number of oocytes retrieved, and number of embryos created by the same woman among the three cycles of treatment. CONCLUSION(S): Consistent ovarian response can be achieved during the first three consecutive IVF cycles.     

Is there a critical endometrioma size associated with reduced ovarian responsiveness in assisted reproduction techniques?

This study investigated the relationships between ovarian endometrioma size, ovarian responsiveness and the number of retrieved oocytes following ovarian stimulation. A prospective study was conducted in a public clinical assisted reproduction centre. A total of 64 infertile women with monolateral endometriomas undergoing IVF or intracytoplasmic sperm injection were included in the study. The total number of follicles, number of follicles ≥16 mm and number of oocytes retrieved of ovaries containing endometrioma and normal ovaries were compared. Multivariate linear regression was used to assess whether number of follicles and collected oocytes varied by endometrioma size, age, basal FSH concentration. Significantly lower numbers of follicles ≥16 mm (P = 0.024) and oocytes retrieved (P = 0.001) in the ovaries containing endometrioma were observed. In patients with endometriomas ≥30 mm, endometrioma size was the most influential contributor to the total number of follicles and oocytes retrieved. Ovarian endometriomas result in reduced response to ovarian stimulation, compared with the response of the contralateral normal ovary in the same individual. In case of endometriomas <30 mm, basal FSH concentration remains the most important prognostic factor for oocyte retrieval.     

单侧输卵管切除术对体外受精-胚胎移植周期卵巢反应性和结局的影响

目的:研究单侧输卵管切除术对体外受精-胚胎移植(IVF-ET)周期卵巢反应性和妊娠结局的影响。方法:以行IVF-ET单侧输卵管切除的106例不孕患者为研究组,同期双侧输卵管梗阻的患者360例为对照组,比较研究组输卵管切除后术侧和健侧超促排卵启动日卵巢的大小和窦卵泡数、hCG注射日卵巢的大小、≥12mm卵泡数和获卵数,同时比较研究组和对照组≥12mm卵泡数、获卵数、受精数、优质胚胎数以及Gn用量、用药天数、妊娠率。结果:研究组中术侧和健侧启动日卵巢的大小无显著性差异,然而超促排卵启动日窦卵泡数、hCG注射日双侧卵巢大小、≥12mm卵泡数和获卵数均有统计学差异。研究组无论是hCG注射日≥12mm卵泡数、获卵数、Gn用量、用药天数,还是受精数、优胚数和妊娠率与对照组比较,均无显著性差异。结论:单侧输卵管切除术降低同侧卵巢的反应性,但总体上不影响卵巢对Gn的反应和IVF-ET妊娠结局。     

Ovarian stromal vascularity is not predictive of ovarian response and pregnancy

The role of ovarian stromal vascularity in the prediction of the ovarian response and pregnancy in infertile women was evaluated by comparing age of women, body mass index (BMI), basal FSH concentration, antral follicle count (AFC) and ovarian stromal vascularity indices measured by three-dimensional power Doppler ultrasound. A total of 111 women in their first IVF cycle were analysed. They were aged <40 years with basal FSH concentration <10 IU/l on recruitment for IVF treatment. AFC, mean ovarian volume and mean ovarian 3D power Doppler flow indices were determined on day 2 of the treatment cycle prior to a standard regimen of ovarian stimulation. Ovarian response was represented by the number of oocytes, serum oestradiol, the duration and dosage of gonadotrophins. AFC achieved the best predictive value in relation to the number of oocytes obtained, followed by age of women and BMI. Basal FSH concentration was the only predictive factor for the duration and dosage of gonadotrophin used. Mean ovarian 3D power Doppler flow indices were not predictive of pregnancy in a multiple logistic regression analysis. Ovarian 3D power Doppler flow indices measured after pituitary down-regulation were not predictive of the ovarian response and pregnancy in the IVF treatment.     

Prognostic factors in controlled ovarian hyperstimulation

OBJECTIVE: To determine whether the number of retrieved oocytes and the required amount of gonadotropins per oocyte in IVF treatment can be predicted with use of the following independent predictive variables: age, parity, cause of infertility, body mass index, day 3-5 FSH, E2, inhibin B, ovarian volume, the number of follicles, and intraovarian and uterine artery vascular resistance measured by ultrasonography before ovarian hyperstimulation. DESIGN: A retrospective analysis. SETTING: University hospital infertility clinic. PATIENT(S): Seventy-four consecutive women attending the university hospital infertility clinic for IVF treatment. INTERVENTION(S): The investigated factors were measured on day 3-5 of the cycle, in which luteal phase suppression was begun before ovarian hyperstimulation preparatory to IVF. MAIN OUTCOME MEASURE(S): The amount of gonadotropins required per oocyte and the number of retrieved oocytes were correlated with the predictive factors in stepwise regression analysis. RESULT(S): The best predictive factors for the number of oocytes retrieved were FSH, inhibin B, and parity, explaining 25% of the ovarian response. Intraovarian vascular resistance, parity, FSH, and inhibin B best predicted the amount of gonadotropins needed, explaining 44% of the variation. CONCLUSION(S): FSH, inhibin B, and parity were the independent predictive factors for the number of retrieved oocytes. The same factors and intraovarian vascular resistance predicted the required amount of gonadotropins per oocyte. The main part of the ovarian response cannot be predicted using the factors investigated.     

Could empirical low-dose-aspirin administration during IVF cycle affect both the oocytes and embryos quality via COX 1–2 activity inhibition?

Purpose

To compare qualitative and quantitative ovarian response in idiopathic infertile women treated with low-dose-aspirin (LDA) during in-vitro-fertilization (IVF) cycles (pl) versus untreated ones.

Methods

We conducted an observational-cohort-study on normo-responders patients aged between 25 and 45 years referred to Assisted-Reproductive Unit - University of Padua – in order to evaluate the ovarian response effects (both qualitative and quantitative) after LDA administration. In detail we aim to assess if LDA administration could improve ovarian response, reducing the gonadotropin administration, and if its administration could increase the amount of follicles greater than 16 mm at pick-up, the amount and quality of oocytes retrieved, the amount and quality of embryos, the chance to achieve a pregnancy and to carry it on.

Results

One hundred six LDA-treated patients (Group-A) and 100 not-treated ones (Group-B) were homogeneous for age and BMI. The Group-A, compared to Group-B, showed higher gonadotropin request, higher number of ovarian follicles at pick-up, more follicles bigger than 16 mm in diameter and more retrieved oocytes (despite higher number of immature and at germinal vesicle stage oocytes) but lower quality of obtained embryos. The comparison between two Groups in term of retrieved oocytes /number of follicles, mature oocytes/retrieved oocytes, fertilized oocytes/mature oocytes and good embryos quality/mature oocytes showed a strongly advantageous ratio for Group-B. For each considered outcome, we found a dose-related effect.

Conclusions

It is mandatory to define which patients could benefit from LDA administration and the adequate timing to administer it since the empirical administration could negatively affect both oocyte and embryo quality during IVF cycles.     

妇科手术对抗苗勒管激素及卵巢储备功能的影响

随着妇科手术方式层出不穷,尤其是微创手术的广泛开展,如何最大限度地保护卵巢储备功能是医患共同关心的话题。卵巢储备功能反映女性的生育能力,是指卵巢内存在的可受精的卵母细胞的数量和质量,评估指标有年龄、基础卵泡刺激素、雌二醇、黄体生成激素、抑制素B、基础窦状卵泡数和卵巢体积等,但是都存在一定的局限性。抗苗勒管激素(anti-Müllerian hormone,AMH)由卵巢的颗粒细胞分泌,在整个月经周期保持相对稳定,测定不受月经周期影响,是预测卵巢储备的可靠指标。综述临床中不同妇科手术对卵巢储备功能的影响。     

Effect of pituitary down-regulation on the ovary before in vitro fertilization as measured using three-dimensional power Doppler ultrasound

OBJECTIVE: To evaluate the changes taking place in the ovaries during pituitary down-regulation. DESIGN: Prospective observational study of women undergoing IVF treatment. SETTING: A tertiary referral center for assisted reproduction. PATIENT(S): Forty women who received the long buserelin acetate treatment protocol.Transvaginal three-dimensional power Doppler ultrasound examinations before and after pituitary down-regulation. INTERVENTION(S): Ovarian volume, number of follicles, vascularization index (VI), flow index (FI), vascularization flow index (VFI), and mean gray value (MG). RESULT(S): Before the pituitary down-regulation, the dominant ovary was larger in volume and had a lower MG than the nondominant ovary. After the down-regulation, there was a significant decrease in the volume and number of follicles and an increase in MG. After pituitary down-regulation, the dominant and nondominant ovaries did not differ from each other in any of the parameters. Polycystic ovaries were larger than normal ones before and after the down-regulation, without any differences in MG, VI, FI, or VFI. Right and left ovaries did not differ from each other after the down-regulation. CONCLUSION(S): The differences observed between dominant and nondominant ovaries seem to disappear after pituitary down-regulation. In addition, polycystic ovaries were always larger than the normal ones, but no differences could be detected in the stromal brightness or vascularity either before or after the administration of GnRH agonist therapy.     

Predictors of poor ovarian response in in vitro fertilization: a prospective study comparing basal markers of ovarian reserve

OBJECTIVE: To identify and quantify predictors of poor ovarian response in in vitro fertilization (IVF). DESIGN; Prospective study. SETTING; Tertiary fertility center. PATIENT(S): One hundred twenty women undergoing their first IVF cycle. INTERVENTION(S): Measurement of the number of antral follicles and the total ovarian volume by ultrasound, and of basal levels of FSH, E(2), and inhibin B on cycle day 3. MAIN OUTCOME MEASURE(S): Ovarian response, and clinical and ongoing pregnancy rates. RESULT(S); The antral follicle count was the best single predictor for poor ovarian response: area under the receiver operating characteristic curve = 0.87. Addition of basal FSH and inhibin B levels to a logistic model with the antral follicle count significantly improved the prediction of poor response; the addition of basal E(2) levels and total ovarian volume did not improve the prediction. To express the discriminative performance of this model toward poor response, a maximum area under the receiver operating characteristic curve of 0.92 was calculated. Poor responders had significantly lower clinical and ongoing pregnancy rates than did normal responders. CONCLUSION(S): Our data demonstrate that the antral follicle count provides better prognostic information on the occurrence of poor response during hormone stimulation for IVF than does the patient's chronological age and the currently used endocrine markers. However, endocrine tests remain informative. Multivariate models can achieve more accurate predictions of outcomes of complex events like ovarian response in IVF.     

Outcome of in vitro fertilization and ovarian response after endometrioma stripping at laparoscopy and laparotomy

OBJECTIVE: To add further data on in vitro fertilization (IVF) outcome and ovarian response after endometrioma stripping via either laparoscopy or laparotomy. STUDY DESIGN: IVF outcome and ovarian response parameters in patients who had undergone unilateral endometrioma stripping at laparoscopy (n=28) or laparotomy (n=10) before IVF were retrospectively compared. RESULTS: Fertilization rates, number of embryos transferred and pregnancy rates did not differ between the groups. Significantly more recombinant FSH was used to induce folliculogenesis, and fewer metaphase II oocytes were retrieved in the laparotomy group. The laparotomy-postcystectomy ovaries were significantly smaller and malpositioned. In both stripping groups, significantly smaller operated-on ovaries with lower numbers of antral and mature follicles were observed as compared to intact ovaries. CONCLUSION: A higher amount of FSH is needed to achieve an acceptable IVF outcome after unilateral endometrioma surgery. Indications for surgical treatment of patients having larger and bilateral cysts with an expectation for future fertility should be cautiously reviewed     

抗苗勒管激素水平与卵巢反应性的相关性分析

目的:探讨育龄期女性抗苗勒管激素(AMH)水平与卵巢反应性的关系。方法:选择第一周期进行体外受精-胚胎移植(IVF-ET)治疗的患者1445例,在启动周期前采用酶联免疫吸附法(ELISA)检测患者血清AMH水平,用超声诊断仪检测卵巢窦卵泡计数(AFC),并结合年龄、体质量指数(BMI)等因素,计算其在卵巢低反应组(获卵数≤3个)和卵巢高反应组(获卵数>15个)的受试者工作特征(ROC)曲线下面积(AUC)。结果:Spearman相关及多元线性回归分析均显示,获卵数与AFC和AMH呈显著正相关(P<0.05),与年龄和方案选择呈显著负相关(P<0.05);多元线性回归分析示获卵数与BMI无明显相关性(P>0.05)。预测卵巢低反应时,AFC和AMH的AUC(分别是0.926和0.883)明显大于BMI和年龄的AUC(分别是0.454和0.181),AMH预测值为1.47μg/L,AFC的预测值为8个。预测卵巢高反应时,AFC和AMH的AUC(分别是0.764和0.759)明显大于BMI和年龄的AUC(分别是0.433和0.389),AMH的预测值为3.35μg/L,AFC的预测值为14个。结论:育龄期女性血清AMH水平与获卵数具有较强的相关性,能独立预测患者的卵巢反应性,且联合超声检测AFC可指导临床医生合理选择促排卵方案,获得优质胚胎,有效指导其生育。