Embryo classification beyond pregnancy: early prediction of first trimester miscarriage using machine learning.

PURPOSE: First trimester miscarriage is a major concern in IVF-ET treatments, accounting for one out of nine clinical pregnancies and for up to one out of three recognized pregnancies. To develop a machine learning classifier for predicting the risk of cleavage-stage embryos to undergo first trimester miscarriage based on time-lapse images of preimplantation development. METHODS: Retrospective study of a 4-year multi-center cohort of 391 women undergoing intra-cytoplasmatic sperm injection (ICSI) and fresh single or double embryo transfers. The study included embryos with positive indication of clinical implantation based on gestational sac visualization either with first trimester miscarriage or live-birth outcome. Miscarriage was determined based on negative fetal heartbeat indication during the first trimester. Data were recorded and obtained in hospital setting and research was performed in university setting. RESULTS: A minimal subset of six non-redundant morphodynamic features were screened that maintained high prediction capacity. Features that account for the distribution of the nucleolus precursor bodies within the small pronucleus and pronuclei dynamics were highly predictive of miscarriage outcome as evaluated using the SHapley Additive exPlanations (SHAP) methodology. Using this feature subset, XGBoost and random forest models were trained following a 100-fold Monte-Carlo cross validation scheme. Miscarriage was predicted with AUC 0.68 to 0.69. CONCLUSION: We report the development of a decision-support tool for identifying the embryos with high risk of miscarriage. Prioritizing embryos for transfer based on their predicted risk of miscarriage in combination with their predicted implantation potential is expected to improve live-birth rates and shorten time-to-pregnancy.

Delineating the heterogeneity of embryo preimplantation development using automated and accurate morphokinetic annotation.

PURPOSE: Our objective was to design an automated deep learning model that extracts the morphokinetic events of embryos that were recorded by time-lapse incubators. Using automated annotation, we set out to characterize the temporal heterogeneity of preimplantation development across a large number of embryos. METHODS: To perform a retrospective study, we used a dataset of video files of 67,707 embryos from four IVF clinics. A convolutional neural network (CNN) model was trained to assess the developmental states that appear in single frames from 20,253 manually-annotated embryos. Probability-weighted superposition of multiple predicted states was permitted, thus accounting for visual uncertainties. Superimposed embryo states were collapsed onto discrete series of morphokinetic events via monotonic regression of whole-embryo profiles. Unsupervised K-means clustering was applied to define subpopulations of embryos of distinctive morphokinetic profiles. RESULTS: We perform automated assessment of single-frame embryo states with 97% accuracy and demonstrate whole-embryo morphokinetic annotation with R-square 0.994. High quality embryos that had been valid candidates for transfer were clustered into nine subpopulations, as characterized by distinctive developmental dynamics. Retrospective comparative analysis of transfer versus implantation rates reveals differences between embryo clusters as marked by poor synchronization of the third mitotic cell-cleavage cycle. CONCLUSIONS: By demonstrating fully automated, accurate, and standardized morphokinetic annotation of time-lapse embryo recordings from IVF clinics, we provide practical means to overcome current limitations that hinder the implementation of morphokinetic decision-support tools within clinical IVF settings due to inter-observer and intra-observer manual annotation variations and workload constrains. Furthermore, our work provides a platform to address embryo heterogeneity using dimensionality-reduced morphokinetic descriptions of preimplantation development.

The effect of hyaluronic acid in embryo transfer media in donor oocyte cycles and autologous oocyte cycles: a systematic review and meta-analysis.

STUDY QUESTION: Does the addition of hyaluronic acid (HA) to embryo transfer medium improve pregnancy outcomes in both autologous and oocyte donation IVF cycles? SUMMARY ANSWER: The best available evidence indicates that the addition of HA to embryo transfer medium is clinically beneficial in cycles with autologous oocytes. WHAT IS KNOWN ALREADY: There is a known clinical benefit of HA addition to embryo transfer media but it is not known if HA affects donor and autologous oocyte cycles differently. STUDY DESIGN, SIZE, DURATION: A systematic review with meta-analysis was performed. The Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL via Cochrane Register of Studies Online (CRSO), MEDLINE, Embase and PsycINFO electronic databases (until 8 January 2020) were searched for randomized controlled trials (RCTs) examining the effect of HA in embryo transfer medium on pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: RCTs with separate donor and autologous oocyte data that compared embryo transfer medium with functional HA concentrations (0.5 mg/ml) to those containing no or low HA concentrations (0.125 mg/ml) were included. Two review authors independently selected trials for inclusion, extracted data and assessed the included studies using the Cochrane risk of bias assessment tool. Pooled risk ratios and 95% CIs were calculated. A summary of findings table was generated using Grading of Recommendations, Assessment, Development and Evaluation criteria. Judgements about evidence quality were justified and incorporated into the reported results for each outcome. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen studies, totalling 4686 participants, were analysed. In autologous oocyte cycles, live birth increased from 32% to 39% when embryo transfer media contained functional HA concentrations (risk ratio (RR) 1.22, 95% CI 1.11-1.34; nine studies, 3215 participants, I2 = 39%, moderate-quality evidence (number needed to treat (NNT) 14). HA-enriched media increased clinical pregnancy and multiple pregnancy rates by 5% and 8%, respectively (RR 1.11, 95% CI 1.04-1.18; 13 studies, 4014 participants, I2 = 0%, moderate-quality evidence, NNT 21) and (RR 1.49, 95% CI 1.27-1.76; 5 studies, 2400 participants, I2 = 21%, moderate-quality evidence, number needed to harm 13). Conversely, in donor oocyte cycles, HA addition showed little effect on live birth and clinical pregnancy (RR 1.12 95% CI 0.86-1.44; two studies, 317 participants, I2 = 50%, low-quality evidence) and (RR 1.06, 95% CI 0.97-1.28; three studies, 351 participants, I2 = 23%, low-quality evidence). There was insufficient available information on multiple pregnancy in donor oocyte cycles and on total adverse effects in both groups to draw conclusions. LIMITATIONS, REASONS FOR CAUTION: There were limited studies with separate data on donor oocyte cycles and limited information on oocyte quality. Additionally, one-third of the included studies did not include the main outcome, live birth rate. WIDER IMPLICATIONS OF THE FINDINGS: There is a moderate level of evidence to suggest that functional HA concentration in embryo transfer medium increases clinical pregnancy, live birth and multiple pregnancy rates in IVF cycles using autologous oocytes. This effect was not seen in donor oocyte cycles, indicating either intrinsic differences between donor and autologous oocytes or lack of statistical power. The combination of HA addition to transfer media in cycles using autologous oocytes and a single embryo transfer policy might yield the best combination, with higher clinical pregnancy and live birth rates without increasing the chance of multiple pregnancies. STUDY FUNDING/COMPETING INTEREST(S): No financial assistance was received. The authors have no competing interests. REGISTRATION NUMBER: N/A.

Hyaluronic acid in embryo transfer media for assisted reproductive technologies.

BACKGROUND: This is an update of a Cochrane Review first published in the Cochrane Library (2010, Issue 7). To increase the success rate of assisted reproductive technologies (ARTs), adherence compounds such as hyaluronic acid (HA) have been introduced into subfertility management. Adherence compounds are added to the embryo transfer medium to increase the likelihood of embryo implantation, with the potential for higher clinical pregnancy and live birth rates. OBJECTIVES: To determine whether adding adherence compounds to embryo transfer media could improve pregnancy outcomes, including improving live birth and decreasing miscarriage, in women undergoing assisted reproduction. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, and PsycINFO electronic databases on 7 January 2020 for randomised controlled trials that examined the effects of adherence compounds in embryo transfer media on pregnancy outcomes. Furthermore, we communicated with experts in the field, searched trials registries, checked reference lists of relevant studies, and conference abstracts were handsearched. SELECTION CRITERIA: Only truly randomised controlled trials comparing embryo transfer media containing functional concentrations of adherence compounds to media with no or low adherence compound concentrations were included. DATA COLLECTION AND ANALYSIS: Two review authors selected trials for inclusion according to the above criteria, after which the same two review authors independently extracted data for subsequent analysis. Statistical analysis was performed according to the guidelines developed by Cochrane. We combined data to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I² statistic. We used GRADE methods to assess the overall quality of evidence for the main comparisons. MAIN RESULTS: We analysed 26 studies with a total of 6704 participants. Overall, the certainty of evidence was low to moderate: the main limitations were imprecision and/or heterogeneity. Compared to embryos transferred in media containing no or low (0.125 mg/mL) HA, the addition of functional (0.5 mg/mL) HA concentrations to the transfer media probably increases the live birth rate (RR 1.21, 95% CI 1.1 to 1.31; 10 RCTs, N = 4066; I² = 33%; moderate-quality evidence). This suggests that if the chance of live birth following no HA addition in media is assumed to be 33%, the chance following HA addition would be between 37% and 44%. The addition of HA may slightly decrease miscarriage rates (RR 0.82, 95% CI 0.67 to 1.00; 7 RCTs, N = 3091; I² = 66%; low-quality evidence). Nevertheless, when only studies with low risk of bias were included in the analysis, there was no conclusive evidence of a difference in miscarriage rates (RR 0.96, 95% CI 0.75 to 1.23; N = 2219; I² = 36%). Adding HA to transfer media probably results in an increase in both clinical pregnancy (RR 1.16, 95% CI 1.09 to 1.23; 17 studies, N = 5247; I² = 40%; moderate-quality evidence) and multiple pregnancy rates (RR 1.45, 95% CI 1.24 to 1.70; 7 studies, N = 3337; I² = 36%; moderate-quality evidence). We are uncertain of the effect of HA added to transfer media on the rate of total adverse events (RR 0.86, 95% CI 0.40 to 1.84; 3 studies, N = 1487; I² = 0%; low-quality evidence). AUTHORS' CONCLUSIONS: Moderate-quality evidence shows improved clinical pregnancy and live birth rates with the addition of HA as an adherence compound in embryo transfer media in ART. Low-quality evidence suggests that adding HA may slightly decrease miscarriage rates, but when only studies at low risk of bias were included in the analysis, the results were inconclusive. HA had no clear effect on the rate of total adverse events. The increase in multiple pregnancy rates may be due to combining an adherence compound and transferring more than one embryo. Further studies of adherence compounds with single embryo transfer need to be undertaken.

Is there a pre-retrieval serum human chorionic gonadotrophin (hCG) threshold level for prediction of subsequent retrieval outcomes and pregnancy in fresh ICSI cycles?

Modern ICSI (intracytoplasmic sperm injection) cycles' outcomes are difficult to predict. Whether human chorionic gonadotrophin (hCG) or luteinizing hormone (LH) serum levels 24 h prior to oocyte retrieval are correlated with retrieval and subsequent cycle results is unclear. An observational historic cohort study of 645 fresh ICSI cycles was conducted. After controlled oocyte stimulation, and 10-12 h after a self-administered trigger, serum levels of hCG (hCG trigger n = 563) and LH (GnRHa trigger n = 82) were measured. Correlations between pre-retrieval hormone levels and cycle results were assessed. No correlation (p > .12) was found between serum pre-retrieval hCG levels or LH levels (in GnRHa-triggered cycles) and total oocytes, M2, M1 + M2 or oocyte maturity rates (OMR) for any of the stimulation protocols. ROC (receiver operator curve) analysis for fertilization rates showed a possible cutoff for LH levels. Pregnancy rates (PR) were higher in rising hCG groups; a cutoff of 117 IU/L was associated with an increase in PR (30.9% to 45.6%) and a moderate sensitivity and specificity (60.6% and 55.0%). However, HCG was not predictive of pregnancy in a logistic regression model. We conclude that preretrieval hCG serum levels are not useful for pre-retrieval estimation of aspiration results but might have a role in prediction of pregnancy.

Oncofertility: insights from IVF specialists-a worldwide web-based survey analysis.

PURPOSE: This research sought to understand IVF-physicians' knowledge of, experience with, and attitudes toward fertility preservation for cancer patients. METHODS: A 35-question, self-report survey request was emailed to IVF providers who were registered on the IVF-Worldwide.com network (3826 clinics). Physicians submitted responses on the IVF-Worldwide.com website. Survey results were reported as a proportion of the responding clinics. RESULTS: Survey responses were completed by 321 (8.4%) globally distributed IVF clinics, representing 299,800 IVF cycles. Of these clinics, 86.6% (278) performed fertility preservation, treating approximately 6300 patients annually. However, 18.4% of the centers reported that patients sought advice independently, without an oncologist's referral. Ovarian tissue cryopreservation was performed by 37.7% of the clinics, yet 52.6% considered the procedure experimental. IVM was performed by 16.5% of responding clinics. A majority (63.6%) of the clinics selected treatment protocols based on each patient's malignancy. Most respondents (76.3%) disagreed that fertility preservation was not yet successful enough to make it an available option. However, 44.2% believed that pregnancy rates following oocyte cryopreservation could not be determined because not enough oocyte cryopreservation patients had completed embryo transfer. CONCLUSIONS: Most clinics performed fertility preservation, tailoring protocols to each patient's disease and condition. Almost 20% of patients sought advice independently, indicating that more effort is needed to encourage oncologists to refer patients. Most survey respondents believed that data was not yet available on either live birth outcomes or the best protocol for each disease. Therefore, long-term study must continue, with the establishment of interim milestones and an outcome-tracking registry.

Worldwide live births following the transfer of chromosomally "Abnormal" embryos after PGT/A: results of a worldwide web-based survey.

PURPOSE: Preimplantation genetic testing for aneuploidy (PGT-A) has become increasingly controversial since normal euploid births have been reported following transfer of embryos diagnosed as "abnormal." There is an increasing trend in transferring "abnormal" embryos; but it is still unknown how many IVF centers transfer "abnormal" embryos and with what efficiency. METHODS: We performed a worldwide web-survey of IVF centers to elucidate PGT-A related practice patterns including transfer of human embryos found "abnormal" by PGT-A. Participating centers reflected in vitro fertilization (IVF) cycles in the USA, Canada, Europe, Asia, South America, and Africa. RESULTS: One hundred fifty-one IVF centers completed the survey; 125 (83%) reported utilization of PGT-A. Europe had the highest utilization (32.3%), followed by the USA and Canada combined at 29.1%. The leading indications for PGT-A were advanced maternal age (77%), followed by recurrent implantation failure (70%), unexplained pregnancy loss (65%), and sex determination (25%); 14% of respondents used PGT-A for all of their IVF cycles; 20% of IVF units reported transfers of chromosomally "abnormal" embryos, and 56% of these took place in the USA, followed by Asia in 20%. Remarkably, 106 (49.3%) cycles resulted in ongoing pregnancies (n = 50) or live births (n = 56). Miscarriages were rare (n = 20; 9.3%). CONCLUSIONS: The transfers of "abnormal" embryos by PGT-A offered robust pregnancy and live birth chances with low miscarriage rates. These data further strengthen the argument that PGT-A cannot reliably determine which embryos should or should not be transferred and leads to disposal of many normal embryos with excellent pregnancy potential.

Preimplantation genetic screening: results of a worldwide web-based survey.

Our objective was to evaluate and characterize the extent and patterns of worldwide usage of preimplantation genetic screening (PGS) among the assisted reproductive technique community. A prospective, web-based questionnaire with questions relating to practices of, and views on, PGS was directed to users and non-users of PGS. A total of 386 IVF units from 70 countries conducting 342,600 IVF cycles annually responded to the survey. A total of 77% of respondents routinely carry out PGS in their clinics for a variety of indications: advanced maternal age (27%), recurrent implantation failure (32%) and recurrent pregnancy loss (31%). Few (6%) offer PGS to all their patients. In most cycles (72%), trophectoderm biopsy is carried out and either array-comparative genomic hybridization (59%) or next-generation sequencing (16%) are used for genetic analysis. Only 30% of respondents regard PGS as clearly evidenced-based, and most (84%) believe that more randomized controlled trials are needed to support the use of PGS. Despite ongoing debate and lack of robust evidence, most respondents support the use of PGS, and believe that it may aid in transferring only euploid embryos, thereby reducing miscarriage rates and multiple pregnancies, increasing live birth rates and reducing the risk of aneuploid pregnancies and births.

Use of various gonadotropin and biosimilar formulations for in vitro fertilization cycles: results of a worldwide Web-based survey.

PURPOSE: The purpose of this study was to identify trends in gonadotropin therapy in patients undergoing in vitro fertilization (IVF) treatment worldwide. METHODS: Retrospective evaluation utilizing the results of a Web-based survey, IVF-Worldwide ( www.IVF-worldwide.com ) was performed. RESULTS: Three hundred fourteen centers performing a total of 218,300 annual IVF cycles were evaluated. Respondents representing 62.2% of cycles (n = 135,800) did not believe there was a difference between urinary and recombinant gonadotropins in terms of efficacy and live birth rate. Of the respondents, 67.3% (n = 146,800) reported no difference between recombinant and urinary formulations in terms of short-term safety and risk of ovarian hyperstimulation syndrome. In terms of long-term safety using human urinary gonadotropins, 50.6% (n = 110,400) of respondents believe there are potential long-term risks including prion disease. For 95.3% of units (n = 208,000), the clinician was the decision maker determining which specific gonadotropins are used for IVF. Of the units, 62.6% (n = 136,700) identified efficacy as the most important factor in deciding which gonadotropin to prescribe. While most (67.3%, n = 146,800) were aware of new biosimilar recombinant FSH products entering the market, 92% (n = 201,000) reported they would like more information. A fraction of respondents (25.6%, n = 55,900) reported having experience with these new products, and of these, 80.3% (n = 46,200) reported that they were similar in efficacy as previously used gonadotropins in a similar patient group. CONCLUSIONS: Respondents representing the majority of centers do not believe a difference exists between urinary and recombinant gonadotropins with respect to efficacy and live birth rates. While many are aware of new biosimilar recombinant FSH products entering the market, over 90% desire more information on these products.

How to define, diagnose and treat poor responders? Responses from a worldwide survey of IVF clinics.

Poor responders represent a significant percentage of couples treated in IVF units (10-24%), but the standard definition of poor responders remains uncertain and consequently optimal treatment options remain subjective and not evidence-based. In an attempt to provide uniformity on the definition, diagnosis and treatment of poor responders, a worldwide survey was conducted asking IVF professionals a set of questions on this complex topic. The survey was posted on www.IVF-worldwide.com, the largest and most comprehensive IVF-focused website for physicians and embryologists. A total of 196 centres replied, forming a panel of IVF units with a median of 400 cycles per year. The present study shows that the definition of poor responders is still subjective, and many practices do not use evidence-based treatment for this category of patients. Our hope is that by leveraging the great potential of the internet, future studies may provide immediate large-scale sampling to standardize both poor responder definition and treatment options.

Irregular cleavage of early preimplantation human embryos: characteristics of patients and pregnancy outcomes.

PURPOSE: This is a retrospective analysis of the morphokinetics, prevalence, and implantation potential of embryos with irregular first and second cleavages as identified by time-lapse microscopy. METHODS: The study included 253 women who underwent 387 assisted reproduction treatments with intracytoplasmic sperm injection (ICSI). Each patient was assigned to one of three groups based on embryo cleavage results. In group I, one to two embryos per cycle showed irregular cleavage; group II, at least three embryos with abnormal cleavage; and in group III (the control group), all embryos cleaved normally. The number of embryos that cleaved from 1 to ≥3 cells or from 2 to ≥5 cells for each patient was recorded. Their prevalence and association with women's characteristics and pregnancy outcome were evaluated. RESULTS: The prevalence of irregular cleavage was 15.6 % among 1772 ICSI embryos. In 101 cycles, 1-2 embryos per cycle showed irregular cleavage (group I). In 32 cycles, at least 3 embryos showed abnormal cleavage (group II). In 254 cycles, all embryos cleaved normally (group III). The average age of the women in group II was significantly lower in comparison with groups I and III (32.5 ± 4.2 vs. 35.1 ± 4.9 and 35.5 ± 5.1, respectively, p < 0.02). In comparison of groups I and II, the odds ratio for ≥3 embryos with irregular cleavage in women younger than 35 was 3.48 (95 % CI, 1.28 to 9.46). Embryos with irregular cleavage were transferred in 16 women. Three live births were achieved following the transfer of single blastocysts derived from embryos with irregular cleavage from two to five cells. CONCLUSIONS: Early embryos with irregular cleavage are significantly more prevalent in younger women. When these embryos develop to the blastocyst stage, they may have normal implantation potential, leading to the birth of healthy babies.

Metformin use in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey.

PURPOSE: To identify trends regarding therapeutic approaches to metformin administration in patients undergoing in vitro fertilization (IVF) treatment worldwide. METHODS: A retrospective evaluation utilizing the results of a web-based survey, IVFWorldwide ( www.IVF-worldwide.com/ ), was performed. RESULTS: Responses from 101 centers performing a total of 50,800 annual IVF cycles was performed. Of these cycles, 10.4% (n = 5,260) reported metformin use during IVF cycles. Indications for metformin use in IVF cycles included polycystic ovary syndrome (PCOS) patients who were habitual abortions (67%), had prior poor egg quality (61%), had high serum insulin levels (56%). Less reported was PCOS with obesity/anvoulation (29%), PCOS with multiple manifestations (23%) and glucose intolerance and insulin resistance (23%). Over half of cycles (54%) treated patients with metformin up to 3 months prior to starting IVF. A majority (82%) of IVF cycles utilized 1500-2000 mg/day of metformin. A nearly equal percentage of centers continued metformin up to a positive ß-HCG test (35%) or to 12 weeks gestation (33%). 70% of IVF cycles reported increased pregnancy rates and decreased miscarriage rates due to the use of metformin. 75% reported the data in the literature is not sufficient for reaching a definitive conclusion concerning metformin treatment in patients undergoing IVF. CONCLUSIONS: While metformin is used worldwide as an adjunct to standard IVF protocols, there is much variation in its use and the majority of centers report lack of evidence supporting its use.

Use of anti-mullerian hormone for testing ovarian reserve: a survey of 796 infertility clinics worldwide.

PURPOSE: The aim of this study is to assess how anti-mullerian hormone (AMH) is used worldwide to test ovarian reserve and guide in vitro fertilization (IVF) cycle management. METHODS: An internet-based survey was sent electronically to registered IVF providers within the IVF-Worldwide.com network. This survey consisted of nine questions which assessed the clinics' use of AMH. The questionnaire was completed online through the IVF-Worldwide.com website, and quality assurance tools were used to verify that only one survey was completed per clinical IVF center. Results are reported as the proportion of IVF cycles represented by a particular answer choice. RESULTS: Survey responses were completed from 796 globally distributed IVF clinics, representing 593,200 IVF cycles worldwide. Sixty percent of the respondent-IVF cycles reported to use AMH as a first line test, and 54 % reported it as the best test for evaluating ovarian reserve. Eighty-nine percent reported that AMH results were extremely relevant or relevant to clinical practice. However in contrast, for predicting live birth rate, 81 % reported age as the best predictor. CONCLUSIONS: AMH is currently considered a first line test for evaluating ovarian reserve and is considered relevant to clinical practice by the majority of IVF providers.

Measurement of antral follicle count in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey.

PURPOSE: The purpose of the present study was to identify trends in the therapeutic approaches used to measure antral follicle count (AFC) in patients undergoing in vitro fertilization (IVF) treatment worldwide. METHODS: A retrospective evaluation utilizing the results of a web-based survey, IVF-Worldwide ( www.IVF-Worldwide.com ), was performed. RESULTS: Responses from 796 centers representing 593,200 cycles were evaluated. The majority of respondents (71.2 %) considered antral follicle count as a mandatory part of their practice with most (69.0 %) measuring AFC in the follicular phase. Most respondents (89.7 %) reported that they would modify the IVF stimulation protocol based on the AFC. There was considerable variation regarding a limit for the number of antral follicles required to initiate an IVF cycle with 46.1 % designating three antral follicles as their limit, 39.9 % selecting either four or five follicles as their limit, and 14.0 % reporting a higher cutoff criteria. With respect to antral follicle size, 61.5 % included follicles ranging between 2 and 10 mm in the AFC. When asked to identify the best predictor of ovarian hyper-response during IVF cycles, AFC was selected most frequently (49.4 %), followed by anti-Mullerian hormone level (42.7 %). Age was selected as the best predictor of ongoing pregnancy rate in 81.7 % of respondents. CONCLUSIONS: While a large proportion of respondents utilized AFC as part of their daily practice and modified IVF protocol based on the measurement, the majority did not consider AFC as the best predictor of ongoing pregnancy rate.

Characterizing the practice of oocyte donation: a web-based international survey.

Although oocyte donation is widely practised, few interventions in this field are evidence based. The objective of this study was to describe the current practices for evaluation and treatment of oocyte donors and recipients worldwide. Through an IVF-focused website, an internet-based survey was addressed to physicians in IVF units worldwide. A total of 161 units responded, reflecting 14,890 annual oocyte donation cycles. The majority (83.3%) of centres perform genetic testing for oocyte donors, and in 94.6% of cycles, donors are <35 years old. Anonymous donors are most commonly used (91.3%) and 95.8% are fresh donations. In 51.4% of donor cycles, the gonadotrophin-releasing hormone (GnRH) antagonist protocol is used, and in 29.8% of these cycles, a GnRH agonist is prescribed for the ovulatory trigger. Recipient pituitary suppression is used in 76.7% of cycles, and oral oestrogen (86.4%) and vaginal progesterone (73.8%) are the preferred routes of administration for endometrial preparation. In the majority (51.5%) of cycles, a minimum endometrial thickness of ≥ 7 mm is required. This study reflects a relative lack of homogeneity in management of oocyte donors and recipients and highlights the need for developing a consensus in the practice of oocyte donation based upon evidence-based medicine.

Luteal-phase support in assisted reproduction treatment: real-life practices reported worldwide by an updated website-based survey.

An updated worldwide web-based survey assessed the real-life clinical practices regarding luteal-phase supplementation (LPS) in assisted reproduction. This survey looked for changes since a former survey conducted nearly 3years earlier. The survey questions were: If you support the luteal phase, when do you start the regimen you are using?; Which agent/route is your treatment of choice to support the luteal phase?; If you use vaginal progesterone, which formulation do you use?; and How long you continue progesterone supplementation if the patient conceived? Data were obtained from 408 centres (82 countries) representing 284,600 IVF cycles/year. The findings were: (i) most practitioners (80% of cycles) start LPS on the day of egg collection; (ii) in >90%, a vaginal progesterone product is used (77% as a single agent and 17% in combination with i.m. progesterone), while human chorionic gonadotrophin as a single agent for LPS is not being used at all; and (iii) in 72% of cycles, LPS is administered until 8-10weeks' gestation or beyond. When compared with the initial survey, the results of this survey are encouraging as there is a clear shift towards a more unified and evidence-based approach to LPS in IVF cycles. This updated worldwide web-based survey assessed the actual real-life clinical practices regarding luteal-phase supplementation (LPS) in assisted reproduction. Specifically, this survey looked for changes since an initial survey conducted nearly 3years earlier. The survey included the following questions: If you support the luteal phase, when do you start the regimen you are using?; Which agent/route is your treatment of choice to support the luteal phase?; If you use vaginal progesterone, which formulation do you use?; and How long you continue progesterone supplementation if the patient conceived? Data from 408 centres in 82 countries representing a total of 284,600 IVF cycles/year were included. Most practitioners (80% of cycles) start LPS on the day of egg collection and in more than 90% a vaginal progesterone product is used for LPS (in 77% as a single agent and in 17% in combination with i.m. progesterone). As a single agent for LPS, human chorionic gonadotrophin is not being used at all. Regarding the duration of supplementation, in 72% of cycles, LPS is administered until 8-10weeks' gestation or beyond. When compared with the initial survey from 2009, the results of this updated survey are encouraging as there is a clear shift towards a more unified and evidence-based approach to luteal-phase support in IVF cycles. Nevertheless, although there is no firm evidence supporting the continuation of LPS after the demonstration of fetal heart beat on ultrasound, this remains the common practice of the majority of assisted reproduction centres worldwide.

Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol).

Previous studies have shown that existing antral follicles in the luteal phase enable ovarian stimulation. In a pilot study, the efficacy of double stimulations during the follicular and luteal phases in women with poor ovarian response was explored (defined according to the Bologna criteria). Thirty-eight women began with mild ovarian stimulation. After the first oocyte retrieval, human menopausal gonadotrophin and letrozole were administrated to stimulate follicle development, and oocyte retrieval was carried out a second time when dominant follicles had matured. The primary outcome measured was the number of oocytes retrieved: stage one 1.7 ± 1.0; stage two 3.5 ± 3.2. From the double stimulation, 167 oocytes were collected and 26 out of 38 (68.4%) succeeded in producing one to six viable embryos cryopreserved for later transfer. Twenty-one women underwent 23 cryopreserved embryo transfers, resulting in 13 clinical pregnancies. The study shows that double ovarian stimulations in the same menstrual cycle provide more opportunities for retrieving oocytes in poor responders. The stimulation can start in the luteal phase resulting in retrieval of more oocytes in a short period of time. This offers new hope for women with poor ovarian response and newly diagnosed cancer patients needing fertility preservation.

Embryo catheter loading and embryo culture techniques: results of a worldwide Web-based survey.

PURPOSE: To identify trends in embryo catheter loading and embryo culture techniques performed worldwide. METHODS: A retrospective evaluation using the results of a web-based survey, (IVF Worldwide ( www.IVF-worldwide.com ), was performed. RESULTS: Responses from 265 centers in 71 countries were obtained. Most centers (97 %) preferred a catheter with its orifice on top, with only 3 % preferring a catheter with the orifice on its side; 41 % preferred a catheter marked for clear ultrasound view. The most commonly-reported methods of embryo loading were medium-air-embryo-air-medium (42 %), medium in catheter with embryo at end (20 %) and medium-air-embryo (15 %). In 68 % of centers the final volume of the catheter was up to 0.3 ml, with only 19 % using 0.3-0.5 ml and 1 % using 0.5-0.7 ml. Using reduced oxygen concentrations for embryo culture was divided between those who used it in combination with the two-gas system (34 %) and those who did not use it at all (39 %); 24 % reported using a three-gas system. Most clinics using reduced oxygen concentrations used it throughout the entire culture period. Half of centers (51 %) reported using reduced oxygen concentrations for the entire IVF population while 6 % reserved it only for blastocyst transfer. The use of sequential media was highly dominant with 40 % reporting its use.

Worldwide survey of IVF practices: trigger, retrieval and embryo transfer techniques.

PURPOSE: To identify common and varying practice patterns used by in vitro fertilization (IVF) providers from a broadly distributed, worldwide survey. Specific information regarding clinical IVF practices involving the oocyte maturation triggering, oocyte retrieval and embryo transfer was elicited. METHODS: This is an internet-based questionnaire study of IVF practices throughout the world. We used 26 multiple choice questions regarding common clinical practices. The data reported are weighted based on the number of IVF cycles performed at the specific IVF center, represented by a single respondent. RESULTS: Surveys were completed from 359 centers in 71 countries throughout the world. The most common practice patterns (defined as ≥75 % of IVF cycles) identified included: use of human chorionic gonadotropin (hCG) for trigger with an antagonist protocol, no routine patient monitoring from hCG trigger to oocyte retrieval, timing oocyte retrieval 34-37 h following oocyte maturing trigger, use of a single lumen retrieval needle, no routine tests following oocyte retrieval prior to patient discharge and use of ultrasound assistance with embryo transfer. CONCLUSIONS: This is the largest and most diversely represented survey of specific IVF practices addressing oocyte maturation triggers, oocyte retrieval and embryo transfers. Several uniform practice patterns were identified that can be correlated with evidence-based medicine; however, we identified multiple variable practice patterns which is likely the result of the absence of definitive evidence to guide IVF practitioners. The results of this survey allow IVF providers to compare their specific practice patterns with those of a global diverse population of IVF providers.

How to recognize PCOS: results of a web-based survey at IVF-worldwide.com.

This retrospective evaluation of a web-based survey posted from 1 to 30 September 2010 was to determine which diagnostic tools physicians are currently utilizing to diagnose polycystic ovary syndrome (PCOS). Responses from 262 IVF centres in 68 countries are included in the study. Providers used various diagnostic criteria to diagnose PCOS, including the Rotterdam criteria (82%), National Institutes of Health criteria (8%), Androgen Excess Society 2006 criteria (3%) and other classification systems (7%). Many providers utilized diagnostic tools not necessarily included in traditional classification systems: 58% of respondents evaluated LH/FSH ratio in addition to androgen concentrations to define patients with PCOS; physicians also commonly obtain measurement of anti-Müllerian hormone (22%) and impaired glucose tolerance (74%) in diagnosing PCOS. Many respondents (64%) felt that polycystic-appearing ovaries on ultrasound with anovulation and a normal serum prolactin should be adequate criteria to diagnose PCOS. In conclusion, while the majority of centres (82%) uses the Rotterdam criteria to diagnose PCOS, other criteria and diagnostic tools are commonly used in evaluating patients with suspected PCOS. This study highlights the need for continual re-evaluation of PCOS diagnostic criteria with an ultimate goal of developing a consensus definition for the disorder in the future.