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Does an association exist between ovarian reserve, ovarian response and embryonic euploidy in female patients under age 35 years?This was a retrospective analysis of intracytoplasmic sperm injection and preimplantation genetic testing for aneuploidies cycles among patients enrolled at Bahceci Fulya IVF Center between January 2016 and August 2019. A total of 133 patients in POSEIDON group 1 (suboptimal responder; female age35 years, antral follicle count [AFC] ≥5, number of oocytes retrieved10) (group A), 133 patients in POSEIDON group 3 (expected low responder; female age35 years, AFC5) (group B) and 323 in the non-low-prognosis group (female age35 years, AFC ≥5 and number of oocytes retrieved9) (group C) were included.There was no significant difference in euploidy rate per embryo among the three groups (61.7% [145/235] for group A versus 53.5% [68/127] for group B versus 62% [625/1008] for group C; P = 0.13). The cancellation rate in cycles without a euploid blastocyst was significantly lower in group C than groups A and B (8.4% versus 12.8% and 16.5%; P = 0.034). Multivariate regression analysis indicated that the ovarian response group did not significantly affect the probability of obtaining a euploid embryo. Trophectoderm score 'C' (odds ratio 0.520, P = 0.007) and inner cell mass score 'C' (odds ratio 0.480, P 0.001) were associated with a decreased probability of obtaining a euploid embryo.These results confirm that POSEIDON group 1 and group 3 and non-low-prognosis patients have different probabilities of euploid embryos being obtained per cycle. However, euploidy rates per embryo are not affected by the patient's ovarian reserve and response.

What is the optimal number of oocytes retrieved at which maximum live birth rate is observed after fresh autologous assisted reproductive technology (ART) cycles for women of different ages?Retrospective cohort study of all fresh autologous ART aspiration cycles (n = 256,643) undertaken in Australia and New Zealand between 2009 and 2015. Primary outcome measure was live birth rate (LBR) (delivery of at least one liveborn baby at 20 weeks' gestation or over per fresh aspiration cycle). Cycles were grouped according to female age (30, 30-34, 35-49, 40-44 and ≥45 years) and ovarian response (one to three, four to nine, 10-14, 15-19, 20-25 and ≥25 oocytes). Secondary outcome was incidence of ovarian hyperstimulation syndrome (OHSS) requiring hospitalization.At different oocyte yields, LBR per fresh aspiration cycle peaked and then declined at, depending on female age:30 years: six to 11 oocytes (LBR 31-34%); 30-34 years: 11-16 oocytes (LBR 29-30%); 35-39 years: nine to 17 oocytes (LBR 21-24%); and 40-44 years: 15-17 oocytes (LBR 11-12%). The incidence of OHSS increased significantly with the number of oocytes retrieved, from 1.2% with 15 oocytes retrieved to 9.3% with 30 or more oocytes retrieved (P0.001).The optimal number of oocytes at which maximum LBR was observed in a fresh aspiration cycle was highly dependent on age. Because of the observational nature of the results, a cause-effect relationship between the number of oocytes retrieved and LBR should not be assumed; evidence from well-designed randomized control trials is required before clinical advice can be suggested.

Research question What level of IVF pregnancy success is currently possible in women of extremely advanced age? Design This study reports on outcomes in women aged 43–51 years at the Centre for Human Reproduction, an academically affiliated private clinical fertility and research centre in New York City. Results During the study years of 2014–2016, 16 pregnancies were established, all through day 3 transfers. Based on ‘intent to treat' (cycle start), clinical pregnancy rates were 4/190 (2.1%), 5/234 (2.1%) and 7/304 (2.3%) and live birth rates were 2/190 (1.1%), 1/234 (0.43%) and 4/304 (1.3%) in 2014, 2015 and 2016, respectively. With reference to embryo transfer, clinical pregnancy rates were 4/140 (2.9%), 5/159 (3.1%) and 7/167 (4.2%) and live birth rates were 2/140 (1.4%), 1/159 (0.63%) and 4/167 (2.4%) for the same years. The results for 2016 also included what are probably the two oldest autologous IVF pregnancies ever reported in the literature. These results were obtained with patient ages, percentage of cycle cancellations and other adverse outcome parameters steadily increasing year by year. Conclusions Female age above 42 is widely viewed as the ultimate barrier to conception with IVF. Data reported here, although small and preliminary, demonstrate that potential outcomes are better than widely perceived, while pregnancy and live birth rates remain significantly inferior to donor egg recipient cycles. However, for selected women at very advanced ages, especially with higher egg/embryo numbers, autologous oocyte IVF offers a better option than widely acknowledged, if they are given individualized age-specific care.

Research question The aim of this study was to investigate how female age affects the predictive effect of sperm DNA fragmentation index (DFI) on clinical outcomes with assisted reproductive technology. Design A total of 2371 patients, comprising 2115 men with a normal DFI (≤30), 256 men with a high DFI (>30) and women of different ages, were recruited and investigated. All patients had normal chromosome karyotypes and were undergoing their first fresh IVF or intracytoplasmic sperm injection (ICSI) cycles. Clinical outcomes were analysed according to the two DFI groups and female age ≤30 and >30 years. Binary logistic regression analysis was performed to identify factors associated with clinical outcome. Results The proportion of couples with at least one good-quality embryo in the DFI ≤30 group was higher than that in the DFI >30 group. When female age exceeded 30 years, clinical pregnancy rate and the proportion of couples with good-quality embryos in the DFI >30 group were lower compared with DFI ≤30; however, there were no differences in outcomes for female age ≤30 years according to DFI. When DFI >30, the cut-off value of female age was 30.5 for detecting clinical pregnancy; the sensitivity was 62.0%, and the specificity was 63.6%. Clinical pregnancy rate and proportion of couples with good-quality embryos were lower in the DFI >30 versus DFI ≤30 group with a female age above 30 years for IVF but not for ICSI. Conclusion Female age has a negative effect and should be considered in predicting the effects of sperm DNA fragmentation on pregnancy outcomes.

The number of embryos available for transfer is significantly lower in PGT-A than in regular IVF simply because of genetic selection. Our aim is to evaluate ovarian reserve and ovarian response in relation to the probability of finding at least one euploid embryo (POE), which is the main determinant for PGT-A success. Over a six-year period, 2011-2017, PGT-A cycles were retrospectively analyzed and 5952 blastocysts were biopsied and diagnosed either by aCGH or NGS. The POE per cycle and the euploidy rate (ER) per diagnosed embryos were evaluated according to maternal age and ovarian reserve as measured by Anti Mullerian Hormone (AMH), day3 Follicle Stimulating Hormone (FSH) levels, and ovarian response as measured by the number of cumulus-oocyte complexes (COCs), metaphase II (MII) oocytes retrieved, top and good quality blastocyst (TQ+GQ) and biopsied blastocysts. According to a logistic regression analysis conducted to correlate maternal age and the ER per cycle, ER decreased by 1.9-fold with each additional year, whereas for POE, the same decline per cycle was around 0.8-fold in a generalized linear mixed model (GLMM) (p In conclusion female age is the most significant predictor of euploidy rate.Euploidy rate does not directly correlate with the number of oocytes retrieved. POE decreases significantly with advancing maternal age. AMH level, d3 FSH levels, the number of COCs, MII oocytes and the number of TQ+GQ and biopsied blastocyst are the main variables affecting POE after adjustment for age indicating that ovarian reserve and response have a significant impact. These findings emphasize the importance of evaluating and counselling the patients for factors both negative and positive, which may affect the success of PGT.

The European Society of Human Reproduction and Embryology published Bologna criteria to generate a definition of poor ovarian responders (PORs). However, there are few data on whether PORs are homogenous for ovarian response or live birth rates (LBRs). In this retrospective study, 821 patients fulfilling Bologna criteria and undergoing intracytoplasmic sperm injection were stratified into four groups: Group A: female age ≥40 with a previous poor response (cycle cancelled or ≤3 oocytes) (105 patients, 123 cycles); Group B: female age ≥40 with an antral follicle count (AFC) < 7 (159 patients, 253 cycles); Group C: AFC

Anti-Mullerian hormone (AMH) has emerged as an important marker of ovarian reserve. Its variation throughout the cycle, however, may still be a matter of debate. The objective of this study was to re-evaluate the intra-cycle fluctuations of AMH in individuals in a prospective clinical study with focus on the age-related effects on these fluctuations. Frequent blood samples were obtained from the mid-luteal phase of the first cycle to the mid-luteal phase of the second cycle in 44 healthy, regularly menstruating Caucasian women. Main outcome measures were individual fluctuations of AMH concentrations during the natural menstrual cycle. AMH concentrations exhibited large fluctuations throughout the cycle and did not follow a defined pattern. Female age was negatively correlated with mean AMH concentrations. The absolute intra-individual variation was also negatively associated with age, whereas the relative intra-individual variation was positively associated with age. Although the fluctuation in relative intra-individual variation was higher in the older group, the absolute variation is very low and these fluctuations might therefore be of limited clinical relevance in this age group. These data show that in younger women caution should be exerted with the interpretation of a single randomly taken AMH measurement as a representative of ovarian reserve. (C) 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved

National registry data provides a valuable resource to quantify factors which influence the outcomes of IVF treatments. Multilevel logistic regression analyses for live birth and multiple births given a live birth were undertaken using data from the UK Human Fertilization and Embryology Authority's registry of treatments conducted between 2000 and 2005. This study analysed 119,930 fresh and 19,918 frozen transfers from 85,349 patients in 84 centres. As well as quantifying the effects of a range of previously identified prognostic factors, the analyses showed that embryo cryopreservation reduced the live birth rate substantially (odds ratio (OR) 0.60, 95% confidence interval (CI) 0.57–0.64) compared with typical fresh cycles. Prognostic factors for transfers following cryopreservation were largely similar to those for fresh cycles, with some evidence that female age is less important, and there were small differences in the effects of the numbers of embryos transferred and previous IVF attempts that can be ascribed to selection effects. No factors were identified which specifically predicted twin outcomes; patients with a high twin risk were those with a high chance of treatment success. After allowing for all prognostic factors, there remained clinically important variability between centres (median OR 1.4) and between patients (median OR 1.8). National registry data provides a valuable resource which can be used to determine to what extent clinical and patient characteristics influence the outcomes of IVF treatments. We fitted complex statistical models for live birth and multiple births to data from the UK national registry of treatments conducted between 2000 and 2005. The analysis included 119,930 fresh and 19,918 frozen transfers from 85,349 patients in 84 centres. As well as quantifying the effects of a range of previously identified prognostic factors, we were able to estimate the magnitude of the losses due to embryo freezing and thawing. The effects of clinical and patient characteristics on the outcomes for frozen transfers were largely similar to those for fresh cycles. No factors were identified which specifically predicted twin outcomes; patients with a high twin risk were those with a high chance of success. After allowing for all the identified prognostic factors, there remained clinically important variability between centres and between patients which may suggest that the patients and clinics differ in their chances of success due to characteristics which are not currently being measured.

This article describes how Androfert complied with the Brazilian Cells and Germinative Tissue Directive with regard to air quality standards and presents retrospective data of intracytoplasmic sperm injection (ICSI) outcomes performed in controlled environments. An IVF facility, composed of reproductive laboratories, operating room and embryo-transfer room, was constructed according to cleanroom standards for air particles and volatile organic compounds. A total of 2060 couples requesting IVF were treated in the cleanroom facilities, and outcome measures compared with a cohort of 255 couples treated at a conventional facility from the same practice before implementation of cleanrooms. No major fluctuations were observed in the cleanroom validation measurements over the study period. Live birth rates increased (35.6% versus 25.8%; P =0.02) and miscarriage rates decreased (28.7% versus 20.0%; P =0.04) in the first triennium after cleanroom implementation. Thereafter, the proportion of high-quality embryos steadily increased whereas pregnancy outcomes after ICSI were sustained despite the increased female age and decreased number of embryos transferred. This study demonstrates the feasibility of handling human gametes and culturing embryos in full compliance with the Brazilian directive on air quality standards and suggests that performing IVF in controlled environments may optimize its outcomes. Regulatory agencies in many countries have issued directives including specific requirements for air quality standards in embryology facilities. This article describes how we complied with the Brazilian Cells and Germinative Tissue Directive with regard to air quality standards. It also presents results of IVF cycles performed in controlled environments. An IVF facility, composed of reproductive laboratories, operating room and embryo transfer room, was constructed according to cleanroom standards for air particles and volatile organic compounds. The cleanest area was the embryology laboratory, followed by the operating room and embryo transfer room. A total of 2060 couples requesting IVF were treated in the cleanroom facilities, and outcome measures compared with a cohort of 255 couples treated at a conventional facility. Live birth rates increased by 37% and miscarriage rates decreased by 30% in the first triennium after cleanroom implementation. Thereafter, the proportion of high-quality embryos steadily increased whereas pregnancy outcomes after ICSI were sustained despite the increased female age and decreased number of embryos transferred. We demonstrate the feasibility of handling human gametes and culturing embryos in full compliance with the Brazilian Directive on air quality standards and suggest that performing IVF in controlled environments may optimize its outcomes.

Objective: Carriers of chromosomal rearrangements have and increased risk for pregnancy losses and repeated failures in IVF cycles. Couples with balanced translocations are usually good candidates for PGD. We have analyzed the results of the embryology laboratory in our public hospital. Material and Methods: Data were collected from March 2001 until February 2010. A total of 28 IVF-PGD cycles were performed. Reciprocal translocations (RecT) were present in 19 cycles (15 of female carriers and 4 of male carriers) and Robertsonian translocation (RobT) in 9 cycles (4 of female carriers and 5 of male carriers). Female age was 34.9±2.5 (mean±SD). A total of 204 embryos were biopsied on day 3 and analyzed for rearranged chromosomes by FISH. Aneuploidy screening was also performed in selected cases. Normal/ balanced embryos were transferred in day 4 or 5. Data obtained in IVF-PGD cycles were analyzed and compared (RecT vs. RobT; male vs. female carriers). Results: No significant differences were observed in the total number of oocytes retrieved, microinjected oocytes and total obtained embryos regarding the type of translocation (RecT vs. RobT). However, for female carriers we obtained more embryos in cycles of RecT than RobT (8.7±3.8 vs. 6.7±1.2; p = 0.03). The total number of unbalanced embryos was higher for RecT than for RobT (5.4±2.4 vs. 3.0±1.3; p = 0.02). This difference was also observed for female carriers (p = 0.04). Seven out the twentyeight IVF-PGD cycles (1 male-RobT; 1 female-RobT; 1 maleRecT and 4 female-RecT) did not have balanced/normal embryos for transfer. In a female-RecT case, transfer was cancelled because normal/balanced embryos had other chromosomal abnormalities. The mean number of normal/balanced embryos transferred was 1.3±1.0 and no statistical differences were observed regarding the type of translocation, nor the sex carrier. Pregnancy rates were slightly better in RobT cycles than in RecT cycles (33.3% vs. 21.0% per cycle; 42.9% vs. 30.7% per transfer), but differences were not significant. Conclusions: Carriers of reciprocal translocation carriers have less favorable prognosis than those with Robertsonian translocations. We have observed more unbalanced embryos in cycles of reciprocal translocations, mainly in female carriers.