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Objective: Various gonadotropins are used for ovarian stimulation (OS). This study investigated the cost-effectiveness of different gonadotropins based on real-world data from the French National Health Database (SNDS) over a 7-year follow-up of assisted reproductive technology (ART) treatments., Design: Cost-effectiveness analysis of different gonadotropins based on real-world data from the SNDS was conducted., Participants: Women from SNDS undergoing OS leading to oocyte pick-up registered between January 31, 2013, and December 31, 2018 (N = 245,534 stimulations), and receiving either recombinant human follicle stimulating hormone (r-hFSH alfa originator; 110,439), its biosimilars (12,287), or urinaries (mainly highly purified human menopausal gonadotropin [HP-hMG; 65,654] and marginally highly purified urinary-human follicle stimulating hormone [7,821]) were included (follow-up: December 31, 2019)., Settings and Methods: Clinical inputs for this model, including live birth (LB) and cumulative LB (CLB) were calculated from data as published in [Best Pract Res Clin Obstet Gynaecol. 2023;88:102308]. A decision-tree model was developed comprising pregnancy and live birth rate (LBR) states for a complete ART cycle, including one fresh and ≤4 frozen/thawed embryo transfers and related costs. Cost inputs included those of drugs, ART procedure, pregnancy and delivery, and adverse events. Cost per LB and CLB and incremental cost-effectiveness ratio (ICER) were assessed. Robustness of results was determined by comprehensive sensitivity analyses., Results: Overall, r-hFSH alfa originator was found to be associated with a lower cost per LB and per CLB (cost per LB: EUR 26,010; CLB: EUR 22,278) versus its biosimilars (cost per LB: EUR 28,037; CLB: EUR 23,807) and versus urinaries (cost per LB: EUR 26,636; CLB: EUR 23,335). Calculated ICERs with r-hFSH alfa for LB were EUR 5,538 and EUR 14,090, whereas for CLB were EUR 1,945 and EUR 13,742 versus biosimilars and urinaries, respectively. Cost-effectiveness acceptability curve showed that in a majority of iterations, r-hFSH alfa originator had a probability of being cost-effective at a hypothetical threshold of EUR 20,000/LB. Sensitivity analyses showed that the most important variable impacting the outcome in fresh transfers was the probability of birth for biosimilars and the probability of pregnancy for urinaries, while for cumulative transfers, it was the probability of pregnancy for biosimilars and the probability of birth for urinaries., Limitations: As the clinical data were obtained from a non-interventional study and not a randomized controlled trial, the results may still be susceptible to residual confounding or other biases., Conclusions: r-hFSH alfa originator is cost-effective compared to its biosimilars and to urinaries (mainly HP-hMG) and is associated with a lower cost per LB compared to these gonadotropins, where the main driver is the higher LB efficacy rate achieved with it., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: To assess the adequate ovarian follicular development and oocyte recovery between ovarian potential (antral follicle count [AFC]) before the start of ovarian stimulation (OS) and oocyte quantity and quality at oocyte retrieval. A holistic overview of the current key performance indicators (KPIs) was applied to identify the complementary strengths and identify where the current repertoire can be expanded., Design: Expert opinion., Setting: Not applicable., Patient(s): Not applicable., Intervention(s): None., Main Outcome Measure(s): To formulate a proposal for a refined and expanded repertoire of KPIs for individualized OS for assisted reproductive technology., Result(s): The performance and outcomes of OS on ovarian follicular development can be evaluated through the application of defined KPIs. Current KPIs for OS are the ovarian sensitivity index, follicular output rate (FORT), oocyte retrieval rate, and follicle-to-oocyte index (FOI). Notably, there are no specific KPIs dedicated to the assessment of follicular development (i.e., recruitment, selection, growth, and dominance). In light of this, we recommend expanding the current KPIs for OS to include "early FORT" (accounting for the number of follicles measuring ≥10 to 11 mm on day 5/6 of OS relative to AFC) and "modified FORT" (the ratio between the number of follicles measuring ≥12 mm at the time of oocyte maturation triggering and AFC); the extension of oocyte retrieval rate to include two discrete categories at oocyte retrieval-follicles measuring ≥12 mm and ≥16 mm-to ensure that all responsive follicles are accounted for; and FOI to be measured at oocyte maturation triggering and oocyte retrieval ("advanced FOI")., Conclusion(s): Once validated and adopted in clinical practice, we envisage that the proposed expanded KPIs measuring the effect of OS on follicular development (recruitment, selection, growth, and dominance) will increase the understanding of the relationship between ovarian reserve, measured by AFC, and oocyte quantity and quality at oocyte retrieval. This understanding will enable physicians to better evaluate the direct effect of different gonadotropins and doses on ovarian response, leading to a more personalized approach to OS in the context of assisted reproductive technology treatment., Competing Interests: Declaration of Interests S.K.S. reports receipt of payment or honoraria for nonpromotional educational lectures from Merck, Ferring, and MSD. J.-E.S. is an employee of Merck Healthcare KGaA, Darmstadt, Germany. R.O. reports receipt of consulting fees from Merck and Ferring and payment or honoraria for lectures from Merck and Ferring. RF has received honoraria for lectures from Merck Healthcare KGaA, Medea and Event Planet. M.H.D. has nothing to disclose. S.C.E. has received unrestricted research grants from Merck KGaA and consulting fees from Merck, Medea, and Event Planet; payment or honoraria for lecture fees from Merck, Sanitanova, Medea, and Event Planet; has a patent on the ART calculator; and is an advisory board member for Nature Reviews Urology (unpaid), Head of the Andrology Committee of the Brazilian Society of Human Reproduction (unpaid), and Co-chair of the Male Infertility Group, WHO Infertility Guidelines (unpaid). M.L. is an employee of Merck Healthcare KGaA, Darmstadt, Germany. T.D. is an employee of Merck Healthcare KGaA, Darmstadt, Germany. C.A. declares receipt of personal fees from Merck, Medea, Event Planet, IBSA, Ely Lilly, and Biogen and payment or honoraria from Merck, Medea, Event Planet, IBSA, and Ferring., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Juan-Enrique Schwarze, Susana Montenegro, and Thomas D’Hooghe are full-time employees of Merck KGaA, Darmstadt, Germany. Vivek Chaudhari is a full-time employee of EMD Serono Inc., USA. Claire Castello-Bridoux is a full-time employee of Merck Santé, France, an affiliate of Merck KGaA, Darmstadt,Germany. Cristina Masseria, and Claudia Roeder are full-time employees of AESARA Europe, Zug, Switzerland.

Research Question: According to real-world data, is recombinant human FSH (r-hFSH) combined with recombinant human LH (r-hLH) or r-hFSH alone more effective for women of advanced maternal age (AMA) in terms of live birth?, Design: Non-interventional study comparing the effectiveness of r-hFSH and recombinant r-hLH (2:1 ratio) versus r-hFSH alone for ovarian stimulation during ART treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register., Results: Overall clinical pregnancy (29.8%, 95% CI 28.2 to 31.6 versus 27.8%, 95% CI 26.5 to 29.2) and live birth (20.3%, 95% CI 18.7 to 21.8 versus 18.0%, 95% CI 16.6 to 19.4) rates were not significantly different between the combined r-hFSH and r-hLH group and the r-hFSH alone group (P = 0.269 and P = 0.092, respectively). Treatment effect was significantly higher for combined r-hFSH and r-hLH compared with r-hFSH alone for clinical pregnancy (33.1%, 95% CI 31.0 to 35.0 versus 28.5%, 95% CI 26.6 to 30.4; P = 0.001, not adjusted for multiplicity) and live birth (22.5%, 95% CI 20.5 to 24.2 versus 19.4%, 95% CI 17.6 to 20.9; P = 0.014, not adjusted for multiplicity) in a post-hoc analysis of women with five to 14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of combined r-hFSH and r-hLH for ovarian stimulation in women aged 35-40 years with normal ovarian reserve., Conclusions: Women of AMA with normal ovarian response benefit from treatment with combined r-hFSH and r-hLH in a 2:1 ratio versus r-hFSH alone in terms of live birth rate. The effectiveness of treatments is best assessed by RCTs; however, real-world data are valuable for examining the effectiveness of fertility treatment, especially among patient groups that are not well represented in clinical trials., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This non-interventional study compared the effectiveness of recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) (2:1 ratio) versus r-hFSH alone for ovarian stimulation (OS) during assisted reproductive technology treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register (D·I·R). Numerically higher clinical pregnancy (29.8% [95% CI 28.2, 31.6] vs. 27.8% [26.5, 29.2]) and live birth (20.3% [18.7, 21.8] vs. 18.0% [16.6, 19.4]) rates were observed with r-hFSH:r-hLH versus r-hFSH alone. The treatment effect was consistently higher for r-hFSH:r-hLH compared with r-hFSH alone in terms of clinical pregnancy (relative risk [RR] 1.16 [1.05, 1.26]) and live birth (RR 1.16 [1.02, 1.31]) in a post-hoc analysis of women with 5-14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of r-hFSH:r-hLH for OS in women aged 35-40 years with normal ovarian reserve., Competing Interests: Declaration of competing interest APB has received honoraria for lectures from Merck Healthcare KGaA, Darmstadt, Germany, and affiliates. JES, DC, ML, and TDH are employees of Merck Healthcare, Darmstadt, Germany. PV was an employee of Merck Healthcare KGaA, Darmstadt, Germany at the time of the study. RF has received honoraria for lectures and an advisory board on the role of LH from Merck Healthcare KGaA, Darmstadt, Germany, and affiliates. BH was an employee of EMD Serono, Rockland, Massachusetts, USA, an affiliate of Merck KGaA, at the time of the study. JK has received honoraria for lectures from Merck Healthcare KGaA, Darmstadt, Germany, and affiliates., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Considerable costs are associated with infertility treatment, but little evidence is available on the main drivers of treatment costs. This cost analysis investigated key costs for treatment with assisted reproductive technology (ART) and the proportion of costs attributed to the acquisition of recombinant human follicle-stimulating hormone (r-hFSH) alfa originator for one fresh embryo transfer (ET) leading to a live birth in Spain, Norway, the UK, Germany, Denmark, South Korea, Australia, and New Zealand. The total costs for one ART cycle with a fresh ET leading to a live birth varied between countries (€4108-€12,314). Costs for pregnancy and live birth were the major contributors in European countries, and the costs of oocyte retrieval, monitoring during ovarian stimulation, pregnancy, and live birth were the top contributors in the Asia-Pacific countries, included in this analysis. Acquisition costs for r-hFSH alfa originator contributed to only 5%-17% of the total costs of one ART cycle with one fresh ET leading to a live birth., Competing Interests: Declaration of Competing Interest RM has received lecture fees and grants from Merck and Ferring; support for attending scientific conferences from Gedeon Richter, Hungary, Merck Healthcare KGaA, Darmstadt, Germany, Angelini, Italy, and Ferring, Switzerland. KFB has received honoraria or consultation fees from Merck Healthcare KGaA, Darmstadt, Germany, Ferring, Switzerland, Bayer, Germany, Stiftung Endometriose Forschung, Germany, and Takeda, Japan and is a member of an advisory board for Merck Healthcare KGaA, Darmstadt, Germany. HK and C-WC declare no relevant conflicts of interest. SI has received personal fees and non-financial support from Merck Healthcare KGaA, Darmstadt, Germany, Ferring, Switzerland, and Gedeon-Richter, Hungary. VC, JES, and TDH are employees of Merck Healthcare KGaA, Darmstadt Germany. CR is an employee of Pharma Value Consulting, Switzerland, and at the time of the study was a consultant for Merck, KGaA Darmstadt, Germany. RM has received a lecture fee from Merck Healthcare KGaA, Darmstadt, Germany; support for attending scientific conferences from Gedeon Richter, Hungary, and Merck Healthcare KGaA, Darmstadt, Germany; and is the Chair of the British Fertility Society., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This comparative non-interventional study using data from the French National Health Database (Système National des Données de Santé) investigated real-world (cumulative) live birth outcomes following ovarian stimulation, leading to oocyte pickup with either originator recombinant human follicle-stimulating hormone (r-hFSH) products (alfa or beta), r-hFSH alfa biosimilars, or urinaries including mainly HP-hMG (menotropins), and marginally u-hFSH-HP (urofollitropin). Using data from 245,534 stimulations (153,600 women), biosimilars resulted in a 19% lower live birth (adjusted odds ratio (OR) 0.81, 95% confidence interval (CI) 0.76-0.86) and a 14% lower cumulative live birth (adjusted hazard ratio (HR) 0.86, 95% CI 0.82-0.89); and urinaries resulted in a 7% lower live birth (adjusted OR 0.93, 95% CI 0.90-0.96) and an 11% lower cumulative live birth (adjusted HR 0.89, 95% CI 0.87-0.91) versus originator r-hFSH alfa. Results were consistent across strata (age and ART strategy), sensitivity analysis using propensity score matching, and with r-hFSH alfa and beta as the reference group., Competing Interests: Declaration of competing interest MG has received fees from Merck Healthcare KGaA, Darmstadt, Germany, as a medical expert for this study, and lecture fees from Merck KGaA, Darmstadt, Germany, MSD, Ferring, IBSA, Gedeon Richter, Theramex, General Electric, Novartis, Besins Healthcare. I-CD has received fees from Merck Healthcare KGaA, Darmstadt, Germany, as a medical expert for this study, and lecture fees from Merck KGaA, Darmstadt, Germany, MSD, Ferring, IBSA, Gedeon Richter, and Theramex. FR and EH are employees of HEVA, Lyon, France. LL, FP, SP, and CC-B are employees of Merck Santé, Lyon, France, an affiliate of Merck KGaA, Darmstadt, Germany. PV, JES, and TDH are employees of Merck Healthcare KGaA, Darmstadt Germany. CH is an employee of Merck KGaA, Darmstadt Germany. MB has received fees from Merck Healthcare KGaA, Darmstadt, Germany, as a medical expert for this study, and lecture fees from Merck KGaA, Darmstadt, Germany., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This was a retrospective real-world evidence analysis of the costs per live birth for reference recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG-HP), based on data from a German in vitro fertilization registry (RecDate). Pregnancy and live birth rates from the RecDate real-world evidence study over three complete assisted reproductive technology (ART) cycles using the same gonadotropin drug were used as clinical inputs. Costs related to ART treatment and to drugs were obtained from public sources. Treatment with r-hFSH-alfa resulted in higher adjusted cumulative live birth rates versus hMG-HP after one (25.3% vs. 22.3%), two (30.9% vs. 27.5%), and three (31.9% vs. 28.6%) ART cycles. Costs per live birth were lower with r-hFSH-alfa versus hMG-HP after one (€17,938 vs. €20,054), two (€18,251 vs. €20,437), and three (€18,473 vs. €20,680) ART cycles. r-hFSH-alfa was found to be a cost-effective strategy compared with hMG-HP over three cycles., Competing Interests: Declaration of competing interest KFB has received honoraria or consultation fees from Merck Healthcare KGaA, Darmstadt, Germany, Ferring, Bayer, Stiftung Endometriose Forschung, and Takeda and is a member of an advisory board for Merck. CR is an employee of Pharma Value Consulting, Switzerland. JES, ML, and TDH are employees of Merck Healthcare KGaA, Darmstadt, Germany. AA was an employee of Merck Healthcare KGaA, Darmstadt, Germany, at the time of the analysis. EF is an employee of IQVIA, Real World Solutions, London, UK. VL is an employee of IQVIA, Real World Solutions, Amsterdam, NL. RF has received honoraria for lectures from Merck Healthcare KGaA, Darmstadt, Germany, and affiliates., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study compared the cost per live birth and cost-effectiveness of the originator recombinant human follicle-stimulating hormone follitropin alfa (r-hFSH-alfa) and r-hFSH-alfa biosimilars for ovarian stimulation prior to assisted reproductive technology treatment in Spain. A decision tree model was developed, comprising pregnancy and live birth for one treatment cycle with fresh embryo transfer. Clinical inputs were based on a recent meta-analysis by Chua et al. [4]. Cost inputs were extracted from publicly available Spanish sources. The costs per live birth were lower with originator r-hFSH-alfa (€18,138) versus r-hFSH-alfa biosimilars (€20,377). The incremental cost-effectiveness ratio was €7208 for originator r-hFSH-alfa versus biosimilars. Drug acquisition costs for originator r-hFSH-alfa represented 10.5% of total costs in the base case analysis, and 6.2% in a treatment cycle resulting in live birth with one fresh embryo transfer. Results from the sensitivity analyses confirmed the robustness of the findings., Competing Interests: Declaration of competing interest SI has received personal fees and non-financial support from Merck Healthcare KGaA, Darmstadt, Germany, Ferring and Gedeon-Richter. EF is an employee of IQVIA Ltd., London, UK. VL was an employee of IQVIA Solutions B.V., Amsterdam, The Netherlands, at the time of the study. CR is an employee of Pharma Value Consulting, Switzerland, and is a consultant for Merck, KGaA Darmstadt Germany. CAV has received personal fees from Merck Healthcare KGaA, Darmstadt, Germany, personal fees, grant, and non-financial support from Merck Healthcare KGaA, Darmstadt, Germany, personal fees and non-financial support from Merck Sharp & Dohme, grant and non-financial support from Ferring, personal fees from Besins, personal fees and non-financial support from Gedeon-Richter, and research funding and non-financial support from Abbott. EAC is an employee of Merck, S.L.U., Madrid, Spain, an affiliate of Merck KGaA. TDH and JES are employees of Merck Healthcare KGaA, Darmstadt, Germany. RM has received personal fees, research funding, grants and non-financial support from Merck Healthcare KGaA, Darmstadt, Germany, and personal fees, grants and non-financial support from Ferring and Gedeon-Richter., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Study Question: Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting?, Summary Answer: Consensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed., What Is Known Already: Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development., Study Design, Size, Duration: Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process., Participants/materials, Setting, Methods: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods., Main Results and the Role of Chance: Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting., Limitations, Reasons for Caution: We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries., Wider Implications of the Findings: A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set., Study Funding/competing Interest(s): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. E.H.Y.N. reports research sponsorship from Merck. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form., Trial Registration Number: Core Outcome Measures in Effectiveness Trials Initiative: 1023., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: To estimate the effectiveness of Atosiban in improving the outcome after embryo transfer. The effectiveness of embryo transfer per cycle is still relatively low. One possible explanation might be uterine contractility that expels the transferred embryos. Atosiban improved the outcome of embryo transfer by reducing uterine contractility., Methods: Data sources: A systematic review of papers in English using MEDLINE and EMBASE (1990-2019). Search terms included Atosiban, embryo transfer. Study selection: We included studies that compared the outcomes of embryo transfer with Atosiban and a control group. Data Extracting: Independent extraction of papers by two authors, using predefined data fields, including study quality indicators., Results: All pooled analyses were based on a fixed-effect model. Four randomised controlled trials, including 1,025 women, and two non-randomised trials, including 686 patients, met our inclusion criteria. In both studies, the heterogeneity was moderate. Atosiban increased clinical pregnancy rates regardless of the indication for ART or type of embryo transferred. Pooled OR in randomized controlled trials reached 1.47 (1.18-1.82), and in non-randomised controlled trials it reached 1.50 (95% CI 1.10-2.05)., Conclusion: Atosiban appears to increase the clinical pregnancy rates in women undergoing embryo transfer.

Research Question: What was the utilization, effectiveness and perinatal outcome of assisted reproductive technologies (ART) performed in Latin America during 2016?, Design: Retrospective collection of multinational data on ART performed in 178 institutions from 15 Latin American countries., Results: This paper reports on 85,474 initiated cycles, 15,070 deliveries and 18,182 babies born in this period. Of all fresh autologous IVF/intracytoplasmic sperm injection (ICSI) cycles, 40.9% were performed in women aged 35-39 years, and 31.1% in women aged ≥40 years. After removing freeze-all cycles, delivery rate per oocyte retrieval was 20.31% for ICSI and 21.85% for IVF. Fresh single embryo transfer including all age categories represented 22.96%, with a 15.35% delivery rate per transfer. Double embryo transfer represented 61.58% of transfers, with a 27.62% delivery rate per transfer. Multiple births included 18.12% twins and 0.55% triplets and higher. In oocyte donation, delivery rate per transfer was 32.89%, with a twin and triplet rate of 23.48% and 0.73%, respectively. Overall, preterm deliveries reached 17.11% in singletons, 65.69% in twins and 95.51% in triplets. Perinatal mortality was 8.0‰ in singletons, 19.0‰ in twins, and 62.3‰ in high-order multiples., Conclusions: The number of initiated cycles continues to increase. Compared with previous years, the number of embryos transferred decreased while the proportion of single embryo transfers increased with a drop in multiple births. It is vital to motivate health care providers and consumers to continue this trend., (Copyright © 2019. Published by Elsevier Ltd.)

Research Question: What was the utilization, effectiveness and safety of assisted reproductive technologies (ART) performed in Latin American countries during 2015, and what were the regional trends?, Design: Retrospective collection of multinational data on assisted reproduction techniques (IVF and intracytoplasmic sperm injection [ICSI], frozen embryo transfer, oocyte donation, preimplantation genetic testing and fertility preservation), from 175 institutions in 15 Latin American countries., Results: In total, 41.25% of IVF/ICSI cycles were performed in women aged 35-39 years, and 28.35% in women aged ≥40 years. After removing freeze-all cycles, delivery rate per oocyte retrieval was 21.39% for ICSI and 24.29% for IVF. Multiple births included 19.58% twins and 0.95% triplets and higher. In oocyte donation, delivery rate per transfer was 36.77%, with a twin and triplet rate of 27.65% and 1.06%, respectively. Overall, preterm deliveries reached 17.38% in singletons, 64.94% in twins and 98.41% in triplets. Perinatal mortality in 14,936 births and 18,391 babies born was 10.5 per 1000 in singletons, 17.9 per 1000 in twins, and 57.1 per 1000 in high-order multiples. Elective single embryo transfer represented 3.11% of fresh transfers, with a 31.78% delivery rate per transfer. Elective double embryo transfer represented 23.3% of transfers, with a 37.79% delivery rate per transfer. Out of 18,391 babies born, 63.22% were singletons, 34.4% twins, and 2.38% triplets and higher., Conclusions: Given the effect of multiple births on prematurity, morbidity and perinatal mortality, reinforcing the existing trend of reducing the number of embryos transferred remains mandatory., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The aim of this review is to determine if the use of DHEA increases the likelihood of success in patients with POR. We searched MEDLINE and EMBASE using the terms "DHEA and diminished ovarian reserve", "DHEA and poor response", "DHEA and premature ovarian aging". A fixed effects model was used and Peto's method to get the odds ratio (OR) with 95% confidence intervals (CI 95%). For quantitative variables, Cohen's method was used to present the standardized mean differences (SMD) with their corresponding confidence intervals. Only five studied fulfilled the selection criteria. DHEA was administered in 25 mg doses, three times a day. In all studies, the authors corrected for the presence of confounding variables such as partner's age, infertility diagnosis and number of transferred embryos. The meta-analysis of the five selected studies assessed a total of 910 patients, who underwent IVF/ICSI, of which 413 had received DHEA. DHEA use was associated with a significant increase in pregnancy likelihood (OR 1.8, CI 95% 1.29 to 2.51, p =0.001). When analyzing the association between DHEA use and the likelihood of abortion, we found low heterogeneity between studies (I 2 =0.0%) and the use of DHEA to be associated to a significant reduction in the likelihood of abortion (OR 0.25, CI 0.07 to 0.95; p =0.045). Analysis of the association of DHEA with average oocyte retrieval showed high variability between studies (I2=98.6%), as well as no association between DHEA use and the number of oocytes retrieved (SMD -0.01, CI 95% -0.16 to 0.13; p <0.05).

The effects of acupuncture on IVF outcomes is still unknown. We carried out a systematic review and meta-analysis of RCT to determine whether acupuncture performed at the time of ET improves outcomes. We searched Medline and Embase from January 1990 to June 2017, for the following terms): (acupuncture; acupuncture therapy) and (reproductive techniques, assisted; in vitro fertilization; embryo transfer). We selected RCT that compared acupuncture with sham acupuncture or no treatment. We included only trials in which acupuncture involved the insertion of needles into traditional meridian points. We evaluated the methodological quality of the trials using the Cochrane risk of bias tool. The measure of treatment effect was the pooled odds ratio of achieving a clinical pregnancy, ongoing pregnancy, or live birth for women in the acupuncture group compared with women in the control group. For pooled data, summary test statistics were calculated using the Mantel-Haenszel method, using the Rev-Man software, version 5.1. We analyzed six studies, including 2,376. In all trials, there were no significant differences between the groups concerning the mean numbers of embryos transferred, the mean age of the women undergoing the procedure, diagnose and use of ICSI. Acupuncture performed the day of ET was associated with a reduced risk of clinical pregnancy (0.87, 95% confidence interval 0.77 to 0.98). The pooled rate difference was -0.06 (-0.12 to -0.01) for clinical pregnancy. None of the trials reported significant adverse effects of acupuncture.

Objective: Preeclampsia (PE) occurs in 4.6% of pregnancies worldwide. The social phenomenon of increasing maternal age has raised the demand for donor oocytes. Egg donation has allowed women with poor ovarian reserve, premature ovarian failure, genetic disorders or surgical menopause to get pregnant. Recipients provide a unique model of immune response because of the differences in the genetic makeup of mothers and fetuses. In PE, immune tolerance may be impaired as a result of having non-autologous eggs implanted. Egg donation is a highly successful assisted reproductive technology, despite the significant number of issues arising from the implantation of non-autologous eggs. This study aimed to determine whether there is an association between egg donation and preeclampsia., Methods: A systematic review of the literature available in PubMed and Google Scholar was carried out from January of 1995 to August of 2016 using the terms 'oocyte donation, preeclampsia', 'oocyte donation, in vitro fertilization, preeclampsia', 'oocyte donation, preeclampsia, outcomes pregnancies', 'oocyte donation, obstetric outcome.' Only six retrospective cohort studies met the selection criteria., Results: The meta-analysis revealed a statistically significant association between egg donation and onset of preeclampsia (OR 4.50; 95% CI: 3.28-6.19; p<0.0001)., Conclusion: Oocyte donation is associated with increased risk of preeclampsia in singleton pregnancies. Therefore, it is crucial to properly record and assess this finding when egg donation is the chosen assisted reproductive technology to attain pregnancy.

Women submitted to ART treatments represent a select subgroup of individuals. Several studies have described the relationship between TAI and pregnancy outcomes as a result of ART, with contradictory results. The purpose of this systematic review was to determine the association between TAI and the risk of miscarriage in pregnancies resulting from ART. MEDLINE via PubMed, LILACS and Embase were searched for studies published in peer-reviewed journals from 1999 to 2017. The studies were summarized using the fixed effects model and the Peto's method to calculate RR in order to flesh out the association between TAI and spontaneous abortion. Only four papers were included in this systematic review and meta-analysis. Thirty-one miscarriages were observed in 210 clinical pregnancies of women with antithyroid antibodies; and 158 miscarriages were seen in 1,371 pregnancies without antithyroid antibodies. The meta-analysis failed to find an association between TAI and higher risk of reproductive loss, RR=0.94 95% confidence interval: 0.71-1.24; p=0.879. In conclusion, the presence of antithyroid antibodies was not associated with increased reproductive loss in patients submitted to ART treatments. It is our opinion that the presence of antithyroid antibodies should be considered as a secondary biomarker of autoimmune disease, rather than an actual cause of miscarriage in patients undergoing ART. Due to the small amount of evidence on the matter, the determination of TAI before the initiation of ART should be limited to research contexts.

Since 1992, the development of intra-cytoplasmic sperm injection (ICSI) has allowed infertile couples and couples affected by severe male factor infertility in particular, many of which with a history of failed traditional IVF, to become parents. This has generated considerable controversy over the safety of the procedure for the offspring. This systematic review seeks to determine whether evidence indicates that the use of ICSI increases the risk of congenital malformation in children born from singleton pregnancies versus naturally conceived children. Twenty-one of the 104 publications listed in the literature search were included in the analysis. Observational studies reported mostly an increased risk for congenital malformation; the risk of congenital malformations is 7.1% in ICSI and 4.0% in the general population (OR 1.99 (95% CI [1.87 - 2.11]). However, attributing higher risk solely to ICSI might seem far-fetched, as in vitro and simulation procedures, patient diseases, and ICSI indication may also be associated with higher risk of malformation.

Multinational data on assisted reproduction techniques undertaken in 2014 were collected from 159 institutions in 15 countries in Latin America. Treatments included IVF/ ICSI, FET, OD, PGD and fertility preservation (FP). 41.34% of IVF/ICSI cycles were performed in women aged 35 to 39 years and 23.35% in women aged 40 and older. After removing cases with total freezing, delivery rate per oocyte retrieval was 25.05% for ICSI and 27.41% for IVF. Multiple births included 20.78% twins and 0.92 % triplets and over. In OD, twins reached 28.93% and triplets 1.07 %. Preterm deliveries reached 16.4% in singletons, 55.02% in twins and 76% in triplets. Perinatal mortality in 18,162 births was 23 per 1000 in singletons, 35 per 1000 in twins, and 36 per 1000 in high-order multiples. Elective single embryo transfer (eSET) represented only 2.63 % of fresh transfers, with a delivery rate of 32.15% per transfer. Elective double embryo transfer (eDET) represented 23.74% of transfers, with a delivery rate of 41.03% per transfer. Among babies born during this period 11,373 (62.6%) were singletons; 6,398 (35.2%) twins, and 391 (2.2%), triplets and more. Given the effect of multiple births on prematurity, morbidity and perinatal mortality, reinforcing the existing trend of reducing the number of embryos transferred is mandatory.

Study Question: Does the use of ICSI offer any outcome advantage over IVF in patients with non-male factor infertility?, Summary Answer: We did not find any outcome improvement that justifies the routine use of ICSI over IVF in non-male factor ART cycles., What Is Already Known: Since its introduction in Latin America, the use of ICSI has increased substantially, even among patients without male factor infertility. However, it is not clear whether ICSI provides an advantage over IVF in non-male factor infertility., Study Design Size Duration: A retrospective cohort study of fresh cycles performed in 155 ART clinics located in 15 Latin American countries between 2012 and 2014. Records were assessed for 49,813 ART cycles (39,564 ICSI and 10,249 IVF) performed in infertile couples who did not have male factor infertility. Student's t -test was used to analyze normally distributed data, Wilcoxon test to analyze non-normally distributed data, and Fisher's exact test for categorical data. Logistic regression was used to quantify the effect of ICSI on delivery rate, adjusting for age of female partner, number of oocytes inseminated, number of embryos transferred, and transfer at blastocyst stage as possible confounding factors. Poisson regression analysis was used to quantify the effect of ICSI on fertilization rate, adjusting for age of female partner., Participants/materials Setting Method: Cycles with the diagnosis of male factor and use of cryopreserved semen and with a freeze-all strategy were excluded., Main Results and the Role of Chance: After correcting for age of female partner, number of oocytes inseminated, number of embryos transferred and transfer at blastocyst stage, we found that the use of ICSI was associated with a significant decrease in the odds of delivery compared to IVF (odds ratio 0.88, 95% CI 0.84 to 0.93; P < 0.0001)., Limitations Reasons for Caution: An important limitation of this study is the lack of randomization owing to its retrospective nature. This could result in selection bias, i.e. couples with the worst prognosis undergoing ICSI, or patients with a history of fertilization failure in IVF cycles undergoing ICSI. More than one cycle from the same couple may be included in the study., Wider Implications of the Findings: The lack of an outcome benefit-and, indeed, a reduced likelihood of delivery-following ICSI in non-male factor infertile couples suggests that ICSI may not be the most appropriate clinical approach in these patients., Study Funding/competing Interests: None.

Objective: The main objective of this study was to assess the prevalence of overweight and obesity among patients undergoing assisted reproductive technology (ART) in Latin America and its consequences on treatment outcomes., Methods: We used the Latin American Registry of ART to obtain women's age and body mass index (BMI), cancellation rate, number of oocytes retrieved and embryos transferred, clinical pregnancy, live birth and miscarriage rates from 107.313 patients undergoing autologous IVF and ICSI during four years; a multivariable analysis was performed to determine the effect of BMI on cancellation, oocytes retrieved, pregnancy, live birth and miscarriage, adjusting for age, number of embryos transferred and embryo developmental stage upon embryo transfer, when appropriate., Results: The prevalence of overweight and obesity was 16.1% and 42.4%, respectively; correcting for age of female partner, overweight and obesity were associated to an increase in the odds of cancellation and to a lower mean number of oocytes retrieved; after adjusting for age, number of embryos transferred and stage of embryo development at transfer, we found that the BMI category was not associated to a change in the likelihoods of pregnancy, live birth and miscarriage., Conclusions: The prevalence of obesity among women seeking ART in Latin America is surprisingly high; however, BMI does not influence the outcome of ART performed in these women.

The last two decades have seen an increase in the number of women diagnosed with infertility. The consequent growth in the use of assisted reproductive technologies (ART) calls for the determination of its long-term effects, including the risk of cancer. Many studies have attempted to answer this question, albeit with contradictory results. This review aimed to assess whether assisted reproductive technologies are associated with an increased risk of gynecological cancer. A search for papers in the literature was carried out on MEDLINE, TRIP DATABASE and NICE, resulting in 11 studies enrolling 3,900,231 patients altogether. Of these, 118,320 were offered ART. The incidence of gynecological cancer in the group offered ART was 0.6%, while the incidence in the group not offered ART was 2.1%. Taking all the studies into consideration, women offered ART were not at greater risk of having gynecological cancer; instead, a protective association was found.

Objective: ART has helped millions of infertile couples worldwide to overcome their childlessness. These successes have been accompanied by an increase in multiple deliveries, and perinatal complications associated. The explanation for this complication is the transfer of more than one embryo, to increase the odds of delivery. Our objective was to compare the outcome of elective dual embryo transfer (eDET) to that of the transfer of more than two embryos without embryo cryopreservation (TET), terms of delivery rate and multiple delivery., Methods: We analyzed the data registered by 155 clinics members of the RLA: 11,024 eDET and 10,634 TET., Results: The delivery rate was significantly higher when eDET was performed than when TET was performed (40.24% and 26.98%, p < 0.001). Also, the ratio of twin deliveries was higher in eDET (25.80% and 20.56%, p < 0.001). However, the ratio of triplets and more deliveries was higher in TET than in eDET (2.34%and 0.52%, p < 0.001). These findings were consistent across the different age categories of the female partner., Conclusion: Our findings suggest that eDET was associated with a statistically significant better delivery rate per embryo transfer, and lower ratio of triplet-and-higher deliveries, regardless of the woman's age. Therefore, there is no evidence that supports the transfer of more than two embryos.

Background: Endometriosis has been described to impair fertility through various mechanisms. However, studies evaluating the reproductive outcomes of women undergoing assisted reproductive technologies show controversial results. The aim of this study is to assess whether the reproductive outcome is impaired among women with endometriosis-associated infertility undergoing IVF., Methods: A retrospective cohort study was performed, including women undergoing IVF reported by the Red Latinoamericana de Reproduccion Asistida (Redlara) registry, between January 2010 and December 2012. The study group included women with endometriosis-associated infertility, and the control group women with tubal factor, endocrine disorders or unexplained infertility. Women above 40 years, severe male factor and premature ovarian failure were excluded. The reproductive outcomes of between both groups were compared. The primary outcome was live birth. Secondary outcomes included clinical pregnancy, miscarriage, number of oocytes retrieved and number of fertilized oocytes. Outcomes were assessed after the first fresh IVF cycle, and were adjusted for age and number of embryos transferred., Results: A total of 22.416 women were included (3.583 with endometriosis and 18.833 in the control group). Mean age of patients in the endometriosis group and control group was 34.86 (3.47) and 34.61 (3.91) respectively, p = 0.000. The mean number of oocytes retrieved were 8.89 (6.23) and 9.86 (7.02) respectively, p = 0.000. No significant differences were observed between groups in terms of live birth (odds ratio (OR) 1.032, p = 0.556), clinical pregnancy (OR 1.044, p = 0.428) and miscarriage rates (OR 1.049, p = 0.623). Women with endometriosis had significantly lower number of oocytes retrieved (incidence risk ratio (IRR) 0.917, 95% CI 0.895-0.940), however, the number of fertilized oocytes did not differ among the two groups when adjusting for the number of oocytes retrieved (IRR 1.003, p = 0.794). An age-stratified analysis was performed, and no differences were observed in the reproductive outcomes between groups for women aged under 35 and 35 to 40., Conclusions: Reproductive outcomes among women undergoing IVF and diagnosed with endometriosis-associated infertility do not differ significantly from women without the disease. Although women with endometriosis generate fewer oocytes, fertilization rate is not impaired and the likelihood of achieving a live birth is also not affected.

Objective: To determine whether the addition of either urinary or recombinant LH in patients undergoing routine clinical care improved the outcome in terms of the number of oocytes recovered for insemination or the delivery rate per initiated cycle., Design: Cohort analysis., Patient(s): Couples undergoing IVF/ICSI in 158 institutions in 15 countries in Latin America., Setting: In vitro fertilization clinics., Intervention(s): We compared the outcome of three different protocols of COH, including rFSH only, rFSH plus rLH, and rFSH plus hMG., Main Outcome Measure(s): The number of mature oocytes recovered and inseminated; proportion of ETs at the blastocyst stage; clinical pregnancy, miscarriage, and delivery rates; proportion of cycles with embryo cryopreservation; and mean number of embryos cryopreserved., Result(s): After correcting for the age of the female partner, body mass index, number of embryos transferred, and stage of embryo development at transfer, we found that LH addition was not associated with an increase in the mean number of metaphase II oocytes inseminated or with an increase in the delivery rate or changes in the miscarriage rate., Conclusion(s): Our study strongly suggests that in routine clinical practice, the type of controlled ovarian stimulation-FSH alone or in combination with LH-has little impact on the outcome of assisted reproductive technology; therefore a more friendly and accessible alternative should be favored., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Multinational data on assisted reproduction techniques undertaken in 2013 were collected from 158 institutions in 15 Latin American countries. Individualized cycle-based data included 57,456 initiated cycles. Treatments included autologous IVF and intracytoplasmic sperm injection (ICSI), frozen embryo transfers, oocyte donations. In autologous reproduction, 29.22% of women were younger than 35 years, 40.1% were 35-39 years and 30.6% were 40 years or older. Overall delivery rate per oocyte retrieval was 20.6% for ICSI and 25.4% for IVF. Multiple births included 20.7% for twins and 1.1% for triplets and over. In oocyte donations, twins reached 30% and triplets 1.4%. In singletons, pre-term births were 7.5%: 36.58% in twins and 65.52% in triplets. The relative risk for prematurity was 4.9 (95% CI 4.5 to 5.3) in twins and 8.7 (95% CI 7.6 to 10.0) in triplets and above. Perinatal mortality was 29.4 per 1000 in singletons, 39.9 per 1000 in twins and 71.6 per 1000 in high order multiples. Elective single embryo transfer represented only 2% of cycles, with delivery rate of 39.1% in women aged 34 years or less. Given the effect of multiple births and prematurity, it is mandatory to reduce the number of embryos transferred in the region., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Embryo cryopreservation is an integral part of assisted reproduction techniques; it allows the sequential transfer of all embryos, thus diminishing the risk of multiple pregnancies and associated perinatal complications. To address concerns about the safety of this procedure, neonatal outcome after 43,070 fresh embryo transfers was compared with 12,068 frozen-thawed embryo transfers (FET). After adjusting for maternal age, gestational age, embryo development at time of transfer, number of babies born and gestational order, FET was not found to be associated with an increase in perinatal mortality (odds ratio [OR] 1.72, 95% confidence interval [CI] 0.81 to 3.62); preterm birth (OR 1.05, 95% CI 0.93 to 1.18); or extreme preterm birth (OR 0.82, 95% CI 0.64 to 1.06). Furthermore, after correcting for known confounding factors, FET was found to be associated with an increase in neonatal weight of 39.7 g (95% CI 1.54 to 64.10; P < 0.0001). Embryo cryopreservation was, therefore, not associated with an increase in the risk of poor perinatal outcome., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Multinational data on assisted reproduction technologies were collected from 155 institutions in 14 Latin American countries during 2012. Case-by-case data included 47,326 assisted reproduction technology cycles covering over 80% of cycles carried out in Latin America. Treatments included IVF, intracytoplasmic sperm injection (ICSI), frozen embryo transfers, oocyte donations and fertility preservation. Embryo transfer and IVF-ICSI was carried out in 39% of women aged 35-39 years and 31% of women aged 40 years or over. Delivery rate per oocyte retrieval was 20.9% for ICSI and 26.5% for IVF. Multiple births comprised 20.6% twins and 1.2% triplets and over. In oocyte donations, twins reached 27.8% and triplets and over 2.4%. Pre-term births in singletons were 14%. The relative risk of prematurity increased by 4.30 (95% CI 4.1 to 4.6) in twins and 43.8 (95% CI 28.5 to 67.4) in triplets and higher. Perinatal mortality increased from 25.2 per thousand in singletons to 44.4 in twins and 80.7 in triplets and over. Elective single embryo transfer was carried out in only 1.4%, of cycles, with a delivery rate of 30% in women 34 years or younger, and should be considered the way forward provided access is facilitated with public funding., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: This report examines information on Assisted Reproduction Technologies performed in Latin America (LA) during 2012., Methods: Multinational data were collected directly from 155 institutions in 14 countries. Individualized, case-bycase data include 47,326 ART cycles covering more than 80% of cycles performed in LA. Treatments included in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), frozen embryo transfers (FET), oocyte donations (OD) and fertility preservation., Results: In 39% of ET IVF/ICSI was performed in women age 35-39 and 31% in women ≥40 years. Delivery rate (DR) per pick-up (OPU) in ICSI and IVF cycles, were 20.9% and 26.5%, respectively. Overall multiple births comprised 20.6% twins and 1.2% triplets. Furthermore, in OD, twins and triplets reached 27.8% and 2.4%, respectively. Pre term births in singletons were 14%. The relative risk of prematurity increased by 4.30 (95% CI 4.1-4.6) in twins, and 43.8 (95% CI 28.5-67.4) in ≥ triplets. Perinatal mortality increased from 25.2‰ in singletons, to 44.0‰ in twins and 80‰ in ≥ triplets. Elective single embryo transfer (eSET) was performed in only 1.4% of cycles with DR of 30% in women ≤34 years., Conclusion: Trends over the last 20 years show that eSET should be the way to go provided access is facilitated with public funding.

Background: Multiple pregnancies are the main complication associated to assisted reproduction, due to the transfer of more than one embryo. Embryo cryopreservation allows the sequential transfer of all generated embryos, thus diminishing the risk of multiple pregnancies. However, it leads to accumulation of cryopreserved embryos. To reduce their accumulation in our unit, we started to preserve embryos as blastocysts, that have a rate of successful pregnancies of approximately 40%., Aim: To perform a sensitivity analysis of this change of policy on the accumulation of embryos., Material and Methods: Records of 571 cycles of in vitro fertilization since 2007 were reviewed, assuming a transference rate of two embryos in women aged less than 35 years and three embryos in older women. The number of embryos that would be preserved as zygotes, eight cell stage or blastocysts, was analyzed., Results: Multiple component logistic regression analysis showed a 20% reduction in the odds ratio of cryopreservation per year of age. There was a 95% reduction in the ratio, when comparing the preservation of third and first day embryos and a 99% reduction when comparing preservation of embryos in blastocyst stage and first day embryos., Conclusions: Cryopreservation at blastocyst stage effectively decreased the frequency of embryo cryopreservation.

Objective: To compare reproductive performance among pregnancies initiated with autologous oocytes and donated oocytes., Design: Retrospective cohort analysis., Setting: Clínica las Condes Hospital, a tertiary referral center in Chile; Fertility, Centro de Fertilizaçao Assistida, Brazil; and 130 institutions reporting to the Latin American Registry (RLA) of assisted reproductive technologies (ART)., Patient(s): Cohort 1 evaluates 70 women who conceived during an IVF cycle, and simultaneously donated fresh oocytes to other 70 oocyte recipients who also conceived. Cohort 2 evaluates the follow-up of 31,550 pregnancies after IVF and 6,024 pregnancies in oocyte recipients, both reported to the RLA between 1995 and 2005., Intervention(s): ART with autologous and donor oocytes., Main Outcome Measure(s): Embryo implantation rate, weight of newborns, gestational age at delivery, perinatal mortality and duration of lactation., Result(s): Oocyte donors and their recipients share similar embryo implantation rate, weight of newborns, gestational age at delivery, perinatal mortality, and duration of lactation., Conclusion(s): The establishment of pregnancy is as efficient with autologous as with donated oocytes. Embryos transferred into their progenitors or in different women have similar chances of implantation, weight at birth, and perinatal outcome. Embryo implantation is affected by the age of the recipient, suggesting that uterine senescence plays a role in fecundity., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

It is agreed that reliability of hormonal products, starting with recombinant technology, has improved uniformity of ovarian response to a specified dosage, and that this has resulted in better pregnancy rates. Nevertheless, IVF cycle cancellation rate has not experienced a substantial decline in the last 5-10 years. We feel that further improvement will be more likely to be achieved once we gain better understanding of factors intrinsic to oocyte biology, such as oocyte ageing and oocyte depletion.

The clomiphene citrate challenge test is a tool to predict ovarian reserve and fertility. It has mainly been used as a predictor of success of IVF/intracytoplasmic sperm injection (ICSI) cycles. Infertile young women with diminished ovarian reserve have a worse prognosis than women with adequate ovarian reserve attempting IVF/ICSI cycles. Nothing is known regarding the outcome of young women with diminished ovarian reserve undergoing low-complexity assisted reproductive treatment such as ovulation induction plus intrauterine insemination (IUI). This study included all women under 37 years who consulted in the authors' centre between May 2004 and August 2005 who underwent ovulation induction and IUI. Ninety-six women younger than 37 years with adequate ovarian reserve, and 50 women with diminished ovarian reserve were found. The pregnancy rate and pregnancy rate per cycle in the adequate ovarian reserve group were significantly higher than those of the diminished ovarian reserve group (46.7% versus 25%, P < 0.02 ; 15.9% versus 7.6%, P < 0.02 respectively). It is concluded that the clomiphene citrate challenge test is a good predictor of low-complexity infertility intervention outcome, and represents an effective tool to establish a prognosis. Therefore, it is very useful in planning therapy, and advising the infertile couple.

Using cDNA microarray methodology, we have shown previously that transcripts of progranulin gene (Grn, also known as acrogranin), a recently identified autocrine growth factor, were upregulated in mouse blastocysts adhered to the filter membrane in an in vitro-culture system. In the present study, we investigated the expression and effects of progranulin on blastocyst hatching, adhesion, and embryo outgrowth during the peri-implantation period in the mouse. During this period, substantial amounts of Grn mRNA were present in both inner cell mass (ICM) and trophectoderm. Progranulin was localized exclusively to the surface of the trophectoderm in early and pre- and postadhesion blastocysts as well as in trophoblast cells and ICM of outgrowth embryos, being secreted as a single, 88-kDa form into the surrounding medium. NIH3T3 cells that had been transfected with a progranulin expression construct secreted the 88-kDa form of the protein, from which a 68-kDa form could be generated by deglycosylation. In vitro treatment of blastocysts with recombinant progranulin promoted blastocyst hatching, adhesion, and outgrowth, whereas rabbit anti-mouse progranulin immunoglobulin G reduced the incidence of blastocyst hatching, adhesion, and outgrowth. Studies of bromodeoxyuridine incorporation and immunodissection of the ICM revealed that progranulin was effective on the trophectoderm but not on the ICM. These results indicate that progranulin is an important factor for the processes of blastocyst hatching, adhesion, and outgrowth, and they suggest that the effects of progranulin on blastocyst adhesion and outgrowth may have been triggered by the previous action of progranulin to induce hatching of the blastocysts.

Background: The prevalence of idiopathic spontaneous premature labor or without an evident clinical cause, has not been reduced with tocolytic treatments, suggesting that premature labor has multiple causes and infections play a not well-defined role., Aim: To perform microbiological studies of the amniotic fluid and of the lower genital tract in women with idiopathic premature labor and intact membranes, relating these findings with maternal and neonatal outcomes., Patients and Methods: Women with pregnancies between 24 and 34 weeks, with premature labor and without an evident clinical cause were enrolled. Amniotic fluid and genital tract samples were obtained for traditional microbiological cultures. This information was related with delivery events and neonatal outcome., Results: Sixty-three patients were included. The overall frequency of microbial invasion of amniotic cavity was 23.8% and of cervical or vaginal infection was 63.5% (in 39.7% there was only cervical or vaginal infection without involvement of the amniotic sac). Absence of infection was documented in 36.5% of women. Compared to patients without infection, women with microbial invasion of amniotic cavity had a higher rate of prematurity (73.3% p < 0.05), a higher rate of prematurity of less than 34 weeks (60% p < 0.01), a higher frequency of preterm rupture of membranes (40% p < 0.001), a shorter admission-to-delivery interval (median 3.0 days p < 0.01) and lower gestational age at delivery (median 33 weeks p < 0.01). Clinical chorioamnionitis and endometritis (20% p < 0.01) was observed only in patients with amniotic cavity infections. Severe asphyxia (26.7% p < 0.05) and neonatal admission to Intensive Care Units (46.7% p < 0.05) were more frequent and neonatal weight was less in the offspring of women with microbial invasion of amniotic cavity (2020 g median p < 0.01)., Conclusions: In preterm labor with intact membranes, intraamniotic infection is the most frequent cause of prematurity and is associated with a higher prevalence of maternal and neonatal problems.