Prediction value of anti-Mullerian hormone (AMH) serum levels and antral follicle count (AFC) in hormonal contraceptive (HC) users and non-HC users undergoing IVF-PGD treatment

Use of hormone contraceptives (HC) is very popular in the reproductive age and, therefore, evaluation of ovarian reserve would be a useful tool to accurately evaluate the reproductive potential in HC users. We conducted a retrospective cohort study of 41 HC users compared to 57 non-HC users undergoing IVF-preimplantation genetic diagnosis (PGD) aiming to evaluate the effect of HC on the levels of anti-Mullerian hormone (AMH), small (2–5?mm), large (6–10?mm) and total antral follicle count (AFC) and the ability of these markers to predict IVF outcome. Significant differences in large AFC (p?=?0.04) and ovarian volume (p?p?18 oocytes were AFC (ROC-AUC; 0.958, p?=?0.001 and 0.883, p?=?0.001) and AMH (ROC-AUC-0.858, p?=?0.01 and 0.878, p?=?0.001), respectively. The predictive values were less significant in non-HC users. These findings are important in women treated for PGD, in ovum donors and for assessing the fertility prognosis in women using HC and wishing to postpone pregnancy.     

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.     

Chronological age vs biological age: an age-related normogram for antral follicle count, FSH and anti-Mullerian hormone

Objective

To evaluate the correlation between chronological and biological age by comparing the normograms of AFC, AMH, and FSH.

Design

Retrospective study

Setting

Data were taken from patients who visited the Infertility Clinic at Dr. Cipto Mangunkusumo General Hospital Jakarta, Indonesia, between January 2008 and December 2010.

Patient(s)

Infertile women who visited the Infertility Clinic.

Intervention(s)

None.

Main Outcome Measure(s)

Normogram of AFC (n = 366), AMH (n = 1616) and FSH (n = 415).

Result(s)

The correlations among AFC, AMH, FSH, and age are statistically significant. Normograms of AFC and AMH with 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles showed a decrease in age where FSH increased. A cut-off value of AFC, AMH, and FSH for poor responders was plotted at the 50th percentile of each normogram. Serum AMH and AFC started to decline in women between 34 and 35 years old. We found a relatively lower slope increase of FSH in older patients compared to that of AFC and AMH. FSH was observed to be a later predictor of biological age than AMH and AFC.

Conclusion(s)

AMH predicted biological age earlier than FSH or AFC. Normograms can provide a reference guide for physicians to counsel infertile women. However, future validation with longitudinal data is still needed.     

Modifying the luteal phase support in natural cycle frozen-thawed embryo transfer improves cycle outcome

Abstract

With the recent trend toward single embryo transfer (ET), cryopreservation of extraneous embryos is becoming increasingly prevalent. Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. All consecutive patients undergoing natural cycle Day-3 FET cycles between May 2012 and March 2015 in our IVF unit were evaluated. While following spontaneous ovulation, all patients received progesterone luteal support. Since June 2014, patients underwent the same aforementioned natural cycle FET cycles, with two additional injections, one of recombinant hCG (250?mcg) and the other of GnRH-agonist (triptorelin 0.1?mg), on the day of transfer and 4?d later, respectively. While the patients' clinical characteristics, the prevalence of embryos that survived the thawing process and the number of embryos transferred were comparable between the earlier as compared with the later period, implantation rate, positive β-hCG, clinical, and ongoing pregnancy rates were significantly higher during the later period. We, therefore, suggest that when natural cycle FET is offered, the addition of two injections of recombinant hCG and GnRH-agonist, on the day of transfer and 4?d later, respectively, might increase clinical pregancy rates. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation.     

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.     

降调节联合激素替代冻融胚胎移植周期中不同内膜转化时间对反复种植失败患者临床结局的影响

目的:探讨反复种植失败(RIF)患者冻融胚胎移植(FET)周期移植时机的选择及对临床结局的影响。方法:选择采用Gn RH-a降调节激素替代方案准备子宫内膜进行FET的RIF患者106例,随机分为A组(常规法)53个周期,即孕酮作用内膜3 d后移植第3日胚胎;B组(改良法)53个周期,即延迟内膜扳机和黄体支持用药,比较组间血清性激素水平、临床妊娠率、早期流产率等相关指标。结果:患者的基本情况组间具有可比性(P0.05);移植日雌二醇(E_2)、孕酮(P)、E_2/P、临床妊娠率组间均有统计学差异(P0.05);移植前1日血清P水平组间差异有统计学意义(P0.05)。结论:对于RIF患者,在降调节联合激素替代-FET周期中,延长雌、孕激素用药时间可刺激内膜达到理想状态,进而获得满意的妊娠结局。     

PCOS患者移植冻融胚胎后妊娠结局

目的:探讨多囊卵巢综合征(PCOS)患者在优质冻融胚胎移植(FET)后是否有更高的妊娠丢失率。方法:回顾性分析诊断为PCOS并初次接受体外受精-胚胎移植(IVF-ET)或卵胞质内单精子注射(ICSI)FET的患者,选择移植冻融胚胎中含有卵裂期优质胚胎且生化妊娠阳性的157个周期的临床资料为PCOS组,同期年龄、体质量指数(BMI)、不孕年限与PCOS组匹配的、因单纯输卵管因素接受IVF-ET助孕治疗并生化妊娠阳性的389个FET周期的临床资料为对照组,比较组间的生化妊娠丢失率、早期流产率、晚期流产率、活产率。结果:在接受优质卵裂期FET的PCOS患者妊娠后,生化妊娠丢失率、早期流产率、晚期流产率、活产率与对照组相比(8.28%vs 5.14%、7.64%vs 8.13%、6.94%vs 5.15%、79.86%vs 84.28%),差异无统计学意义(P0.05)。结论:在固定胚胎质量这个重要的影响妊娠早期丢失的影响因子的基础上,排除年龄、BMI、自然流产次数、是否多胎妊娠、移植日内膜厚度等影响因素的干扰,患PCOS并不增加IVF/ICSI的生化妊娠丢失率和临床妊娠流产率。     

The use of anti-Müllerian hormone and antral follicle count to predict the potential of oocytes and embryos

Objective

To investigate whether anti-Müllerian hormone (AMH) is better than antral follicle count (AFC) in predicting oocyte yield and embryo quality after controlled ovarian hyperstimulation for in vitro fertilization (IVF).

Study design

This is a prospective observational study involving 162 women (<40 years old) undergoing their first IVF cycle at an IVF unit within a university hospital. AMH and AFC measurements were made on day 3 of the cycle within 3 months of starting ovarian stimulation. A standard long down-regulation protocol using gonadotrophin releasing hormone agonist and recombinant follicle stimulating hormone was used. A maximum of two embryos were transferred on day 2 or 3 following oocyte retrieval. The primary outcome was the number of good quality embryos available for transfer and freezing. Embryos were graded according to the number of blastomeres, the difference in blastomere size and the degree of fragmentation, into grades 1–4. Secondary outcomes included the number of oocytes retrieved and fertilized and the live birth rate. Correlation between different parameters was calculated using Spearman's correlation coefficient. Receiver operating characteristic (ROC) curves were generated for AMH and AFC to compare ability of parameters to predict top quality or frozen embryos and the occurrence of a live birth.

Results

Of the 137 women who had fresh embryo transfer, 52 became pregnant (32.1% pregnancy rate per cycle started) and 38 had a live birth (23.5% live birth rate per cycle started). Both AMH and AFC had highly significant correlations with the number of oocytes retrieved and the number of oocytes fertilized (P < 0.001). The two markers were also significantly associated with the number of top quality embryos available for transfer and the number of embryos frozen (P < 0.01). With regard to live birth, AMH performed better than AFC (P < 0.01 and P < 0.05, respectively), but both markers were more valuable in predicting the absence rather than the occurrence of live birth (negative predictive value 84%).

Conclusions

AMH and AFC are comparable predictors of oocytes retrieved and of the number of good quality embryos available for transfer and freezing. Prediction of live birth may help clinicians selecting patients suitable for single embryo transfer.     

自然周期准备内膜在子宫内膜异位症患者冻融胚胎移植中的结局分析

目的:研究以自然周期作为子宫内膜准备方式对子宫内膜异位症(EMS)患者冻融胚胎移植(FET)妊娠结局的影响。方法:回顾性分析EMS患者353个FET周期,按EMS严重程度分组,A组:I~II期,120个周期;B组:III~IV期,233个周期;另将B组中囊肿复发的47个周期设为D组;而将输卵管因素不孕患者的300个FET周期纳入为对照组(C组),比较A、B、C组患者自然周期准备内膜的妊娠结局。结果:A、B、C组患者的种植率、活产率、继续妊娠率、流产率、妊娠期并发症率无统计学差异(P0.05),且妊娠结局与EMS的分期无关。A、B、C组均没有出生缺陷儿。当高质量的胚胎移植时,卵巢内膜异位囊肿并不影响妊娠结局。B组较C组低出生体质量儿和早产儿的发生率高。结论:EMS患者自然周期准备内膜与输卵管性因素不孕患者有相似的妊娠结局,且与EMS严重程度无关,妊娠结局不受内膜异位囊肿的影响,是经济、高效的内膜准备方法。     

Application of atosiban in frozen-thawed cycle patients with different times of embryo transfers

This prospective cohort study aimed to examine the effects of atosiban, given before transfer of frozen-thawed embryo to women with different number of embryo transfer (ET) cycles. Atosiban treatment significantly increased implantation rate and clinical pregnancy rate in the third and more than three ET groups. However, there were no significant increases in the above parameters in the first and second ET groups. Our study showed that patients those who underwent the third or more than three ET cycles were inclined to higher uterine contractions and serum oxytocin level, thus atosiban treatment starting from the third ET cycle may be effective in improving embryo implantation. This is the first study to evaluate the optimal atosiban treatment window corresponding to the number of ET cycles of the patients.     

Inter-cycle and inter-observer variability of the antral follicle count in routine clinical practice

Antral follicle count (AFC) is a reliable predictor of ovarian response to stimulation and its inter-cycle and inter-observer variability has been extensively studied on in vitro fertilization (IVF), mostly in highly selected populations within studies not originally designed for this purpose. In this retrospective cohort study, we assess the inter-cycle variation of AFC in a setting similar to that of the daily practice. We included only patients undergoing mild stimulation for intrauterine insemination (IUI). One hundred and forty-eight patients had two (62 patients, group A), three (49 patients, group B) or four (37 patients, group C) IUI cycles and AFC was measured on early follicular phase of each cycle by one of the members of the medical team within daily practice. Intra-class correlation coefficients were used to estimate variability. Inter-cycle variability rendered ICCs above 0.70 in all groups improving along with the number of cycles [Group A ICC 0.78 (95%CI 0.66–0.86), Group B ICC 0.87 (95%CI 0.80–0.92) and Group C ICC 0.91 (95%CI 0.85–0.95)]. Inter-observer variability showed a high degree of concordance with ICCs above 0.95. We provide the closest approximation to real inter-cycle and inter-observer AFC variability expected in routine clinical practice.     

Effect of mid-luteal phase GnRH agonist on frozen-thawed embryo transfers during natural menstrual cycles: a randomised clinical pilot study

This prospective randomised crossover study evaluated the effect of mid-luteal single-dose gonadotropin-releasing hormone agonist (triptoreline) on pregnancy outcomes in natural-cycle frozen embryo transfers (FETs). Ninety-eight women were randomised to receive either standard luteal support with vaginal micronised progesterone or an additional single dose of 0.1?mg triptoreline at the time of implantation. The intervention group was composed of 65 FET cycles and the control group of 62 cycles. In the intervention group, there were more positive pregnancy tests, clinical pregnancies and live births, but the differences did not reach statistical significance. The mean beta human chorionic gonadotropin (β-hCG) concentration of singleton pregnancies was significantly lower in the intervention group compared to the control group (p?=?0.048). No difference was detected in the median birth weight of the newborns.     

Follicle recruitment determines IVF productivity rate via the number of embryos frozen and subsequent transfers

IVF productivity rate is an index defined as the sum of all live births from either fresh or frozen embryo transfers arising from a single oocyte collection. This retrospective analysis over 9 continuous years used this index to understand the potential impact on pregnancy rates of milder stimulation regimens with associated reduced egg numbers. The productivity rate per collection increased in a linear and significant rate as more oocytes were recovered, more embryos frozen and more frozen embryo transfers contributed to pregnancy. This observation was true for women aged <35 years and less so for women aged 35–39 years but not for women aged 40 years and older. The contribution of frozen embryo transfer to the productivity rate rose in a linear manner, reaching over 40% of all live births with nine oocytes. The number of live births per oocyte, pronuclear embryos and thawed embryos decreased significantly but the number of live births per embryo transferred (fresh or frozen) rose with rising oocyte numbers, reflecting increasing opportunity for embryo selection. This study suggests that optimal benefits with minimal risks are gained from a model that includes both fresh and frozen transfers under stimulation generating between 8 and 12 eggs.Most of the costs and risks associated with an IVF cycle occur during the stimulation, egg collection and subsequent transfer of fresh embryos and ignore or treat separately the outcome from any subsequent frozen embryo transfers. We have used the term ‘productivity rate’ (or cumulative pregnancy rate per collection cycle) that includes outcomes from both fresh and frozen transfers as a tool to explore the impact of oocyte numbers on the ultimate chance of pregnancy. While the pregnancy rate for individual fresh and frozen transfers were largely unrelated to oocyte numbers, the cumulative chance of pregnancy rose significantly with the number of oocytes recovered. This was due to the increasing contribution of frozen embryo transfers to the overall chance of pregnancy producing more than half of all pregnancies above five oocytes. While the fertilization rate and embryo quality was independent of egg numbers, increasingly more embryos needed to be used to generate sufficient good-quality embryos for transfers as the egg numbers rose. The study found that 8–12 oocytes provided the highest cumulative chance of pregnancy with the least risk of either failed fertilization or ovarian hyperstimulation syndrome and this range could be used as a target number for individualized stimulation regimens.     

Anti-Mullerian hormone and antral follicle count as predictors for embryo/oocyte cryopreservation cycle outcomes in breast cancer patients stimulated with letrozole and follicle stimulating hormone

Purpose  

To predict embryo/oocyte cryopreservation cycle (ECC) outcomes in breast cancer patients stimulated with letrozole and follicle stimulating hormone for fertility preservation based on observed anti-mullerian hormone (AMH) levels and antral follicle counts (AFC).