The definition presented here represents the first realistic attempt by the scientific community to standardize the definition of poor ovarian response (POR) in a simple and reproducible manner. POR to ovarian stimulation usually indicates a reduction in follicular response, resulting in a reduced number of retrieved oocytes. It has been recognized that, in order to define the poor response in IVF, at least two of the following three features must be present: (i) advanced maternal age or any other risk factor for POR; (ii) a previous POR; and (iii) an abnormal ovarian reserve test (ORT). Two episodes of POR after maximal stimulation are sufficient to define a patient as poor responder in the absence of advanced maternal age or abnormal ORT. By definition, the term POR refers to the ovarian response, and therefore, one stimulated cycle is considered essential for the diagnosis of POR. However, patients of advanced age with an abnormal ORT may be classified as poor responders since both advanced age and an abnormal ORT may indicate reduced ovarian reserve and act as a surrogate of ovarian stimulation cycle outcome. In this case, the patients should be more properly defined as 'expected poor responder'. If this definition of POR is uniformly adapted as the 'minimal' criteria needed to select patients for future clinical trials, more homogeneous populations will be tested for any new protocols. Finally, by reducing bias caused by spurious POR definitions, it will be possible to compare results and to draw reliable conclusions.

/pdf/eshre-consensus-on-the-definition-of-poor-response-to-1caz0hdbpu.pdf

ESHRE consensus on the definition of ‘poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria

pared. RESULTS: AMH predicts live birth [contribution to variance (CTV) 3.84%, P< 0.001] and oocyte yield (r 5 0.71, P< 0.0001, CTV 7.3%, P< 0.0001). Compared with age and FSH, AMH performs better in prediction of live births [area under receiver operating characteristic curve (AUC) 0.62, 95% CI 0.55–0.68; FSH AUC 0.42, 95% CI 0.35–0.49; age AUC 0.48, 95% CI 0.41–0.55, P 5 0.0028] and excessive response to ovarian stimulation (AMH AUC 0.90, 95% CI 0.83–0.96; FSH AUC 0.32, 95% CI 0.23–0.40; age AUC 0.57, 95% CI 0.43–0.71, P< 0.001). AMH prediction of oocyte yield is independent of age (r 52 0.28, P< 0.0001, CTV 1.4%, P 5 0.006), however, a significant negative interaction (CTV 3.6%, P< 0.0001) exists. AMH demonstrates improved differential distributions for non-, poor, normal and excessive ovarian responses relative to FSH and age. CONCLUSIONS: Plasma AMH is a superior predictor of live birth and anticipated oocyte yield compared with FSH and age, facilitating individualization of therapy prior to first ART cycle.

Serum anti-Müllerian hormone and FSH: prediction of live birth and extremes of response in stimulated cycles—implications for individualization of therapy

Context: Women with breast cancer are not typically offered embryo or oocyte cryopreservation to preserve their fertility before chemotherapy because of the potential risks associated with high estrogen levels arising from ovarian stimulation. Objective: We aimed to determine whether the combination of an aromatase inhibitor with gonadotropin treatment in breast cancer patients produces comparable results to standard in vitro fertilization (IVF), without a significant increase in estradiol levels and delay in the initiation of chemotherapy. Patients and Methods: Stages I-IIIA breast cancer patients (n = 47) received 5 mg/d letrozole and 150–300 IU FSH to cryopreserve embryos or oocytes. Age-matched retrospective controls (n = 56) were selected from women who underwent IVF for tubal disease. Results: Whereas letrozole and FSH stimulation resulted in significantly lower peak estradiol levels (mean ± sd 483.4 ± 278.9 vs. 1464.6 ± 644.9 pg/ml; P < 0.001) and 44% reduction in gonadotropin requirement, compared...

/pdf/letrozole-reduces-estrogen-and-gonadotropin-exposure-in-2bhm28jl9p.pdf

Letrozole reduces estrogen and gonadotropin exposure in women with breast cancer undergoing ovarian stimulation before chemotherapy.

Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial.

Context: For the last 40 yr, the first line of treatment for anovulation in infertile women has been clomiphene citrate (CC). CC is a safe, effective oral agent but is known to have relatively common antiestrogenic endometrial and cervical mucous side effects that could prevent pregnancy in the face of successful ovulation. In addition, there is a significant risk of multiple pregnancy with CC, compared with natural cycles. Because of these problems, we proposed the concept of aromatase inhibition as a new method of ovulation induction that could avoid many of the adverse effects of CC. The objective of this review was to describe the different physiological mechanisms of action for CC and aromatase inhibitors (AIs) and compare studies of efficacy for both agents for ovulation induction. Evidence Acquisition: We conducted a systematic review of all the published studies, both controlled and noncontrolled, comparing CC and AI treatment, either alone or in combination with gonadotropins, for ovulation induc...

Aromatase Inhibitors for Ovulation Induction

In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study

https://www.fertstert.org/article/S0015-0282(05)00598-4/pdf

The aromatase inhibitor letrozole increases the concentration of intraovarian androgens and improves in vitro fertilization outcome in low responder patients: a pilot study.

BACKGROUND It has been reported that a natural cycle (NC) is similar to or even better than hormone replacement therapy (HRT) in patients with regular cycles who undergo frozen embryo transfer (FET). Hundreds of FETs are managed yearly in our clinic. Scheduling these cycles is critical in a busy unit like ours. This is why we have to prove if a NC really shows a better outcome than other endometrium preparation protocols. METHODS Hence we carried out a prospective study between June 2011 and June 2012, which included 530 patients (570 FET cycles) randomly allocated to two study groups: Group 1 (n=280 cycles), artificial cycle (HRT); or group 2 (n=290 cycles), natural cycle. Natural cycles were later divided into two groups: 169 patients scheduled with human chorionic gonadotropin (hCG) and 121 with endogenous luteinizing hormone (LH) surge. The inclusion criteria were: age <39 years, regular menstrual cycles (26-35 days), and previous IVF cycle with embryo cryopreservation. The exclusion criteria were polycystic ovarian syndrome and endometriosis stage III/IV. RESULTS No statistical differences were found in the baseline characteristics among groups, nor between implantation or ongoing pregnancy rates (30.8% HRT group; 32.7% hCG group; 34.5% LH surge group). However, a higher miscarriage rate was observed in the HRT group when compared to hCG or LH surge (21.2% versus 12.9% versus 11.1%, P<0.01). Live birth rates were similar among groups, as were perinatal outcomes, for rates of natural delivery and weight and length of newborns. CONCLUSIONS We conclude that scheduling FET with HRT on weekdays and avoiding work overload at weekends prove efficient and safe in cycle outcome terms. Another reason for the convenience of an HRT protocol is having fewer visits to the clinic compared to natural cycle protocols.

/pdf/impact-of-endometrial-preparation-protocols-for-frozen-2hxvua9bw0.pdf

Impact of Endometrial Preparation Protocols for Frozen Embryo Transfer on Live Birth Rates.

Chromosome abnormalities in embryos obtained through in-vitro maturation (IVM) of oocytes from 11 oocyte donors were compared with embryos from women undergoing fluorescence in-situ hybridization (FISH) analysis for sex selection. Thirtythree oocytes had reached metaphase II stage at 28–30 h (65%) and 27 were successfully fertilized by intracytoplasmic sperm injection. Blastomere biopsy was performed in 20 embryos (74%). For five embryos, two blastomeres were analysed, three of which were mosaic. FISH study revealed aneuploidies of chromosomes 13, 15, 16, 18, 21, 22, X and Y in 12 embryos (60%) and euploidy in the remaining eight (40%). The percentage of aneuploidies in the control group was 33%. Differences between IVM and control embryos were not statistically significant. The high incidence of chromosome abnormalities in embryos resulting from the IVM protocol may account for the low implantation rates reported by others. Although a greater incidence of miscarriage or congenital abnormalities in babies born alive following IVM versus conventional IVF has not been observed in previous studies, preimplantation genetic aneuploidy screening or prenatal chromosome studies may be recommended to these patients on the basis of the present results.

https://www.rbmojournal.com/article/S1472-6483(10)60026-0/pdf

A. Guillen

Papers

In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study

The aromatase inhibitor letrozole increases the concentration of intraovarian androgens and improves in vitro fertilization outcome in low responder patients: a pilot study.

Impact of Endometrial Preparation Protocols for Frozen Embryo Transfer on Live Birth Rates.

The impact of in-vitro maturation of oocytes on aneuploidy rate.

Improvement of clinical outcome in severe male factor infertility with embryo selection based on array-CGH: a randomized controlled trial