An OHSS-Free Clinic by segmentation of IVF treatment
TL;DR: The syndrome can be erased by applying ovarian stimulation using the combination of GnRH antagonist with GnRH agonist to trigger ovulation, and the strategy is to freeze all of the oocytes or embryos for later use.
Abstract: Published data indicate a significant increase in ovarian hyperstimulation syndrome globally. The occurrence of approximately three maternal deaths per 100,000 stimulated women has been reported, and extrapolation of these figures to a global situation would give an impressive number. The syndrome can be erased by applying ovarian stimulation using the combination of GnRH antagonist with GnRH agonist to trigger ovulation. In this case, the strategy is to freeze all of the oocytes or embryos for later use.
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TL;DR: Systematic collection and dissemination of international ART data allows patients, health professionals, and policy makers to examine and compare the impact of reproductive strategies or lack of them as markers of reproductive health.
498 citations
TL;DR: A systematic review and meta-analysis of clinical outcomes following slow-freezing/thawing versus vitrification/warming of oocytes and embryos is provided to inform the development of World Health Organization guidance on the most effective cryopreservation method.
Abstract: BACKGROUND Successful cryopreservation of oocytes and embryos is essential not only to maximize the safety and efficacy of ovarian stimulation cycles in an IVF treatment, but also to enable fertility preservation. Two cryopreservation methods are routinely used: slow-freezing or vitrification. Slow-freezing allows for freezing to occur at a sufficiently slow rate to permit adequate cellular dehydration while minimizing intracellular ice formation. Vitrification allows the solidification of the cell(s) and of the extracellular milieu into a glass-like state without the formation of ice. OBJECTIVE AND RATIONALE The objective of our study was to provide a systematic review and meta-analysis of clinical outcomes following slow-freezing/thawing versus vitrification/warming of oocytes and embryos and to inform the development of World Health Organization guidance on the most effective cryopreservation method. SEARCH METHODS A Medline search was performed from 1966 to 1 August 2016 using the following search terms: (Oocyte(s) [tiab] OR (Pronuclear[tiab] OR Embryo[tiab] OR Blastocyst[tiab]) AND (vitrification[tiab] OR freezing[tiab] OR freeze[tiab]) AND (pregnancy[tiab] OR birth[tiab] OR clinical[tiab]). Queries were limited to those involving humans. RCTs and cohort studies that were published in full-length were considered eligible. Each reference was reviewed for relevance and only primary evidence and relevant articles from the bibliographies of included articles were considered. References were included if they reported cryosurvival rate, clinical pregnancy rate (CPR), live-birth rate (LBR) or delivery rate for slow-frozen or vitrified human oocytes or embryos. A meta-analysis was performed using a random effects model to calculate relative risk ratios (RR) and 95% CI. OUTCOMES One RCT study comparing slow-freezing versus vitrification of oocytes was included. Vitrification was associated with increased ongoing CPR per cycle (RR = 2.81, 95% CI: 1.05-7.51; P = 0.039; 48 and 30 cycles, respectively, per transfer (RR = 1.81, 95% CI 0.71-4.67; P = 0.214; 47 and 19 transfers) and per warmed/thawed oocyte (RR = 1.14, 95% CI: 1.02-1.28; P = 0.018; 260 and 238 oocytes). One RCT comparing vitrification versus fresh oocytes was analysed. In vitrification and fresh cycles, respectively, no evidence for a difference in ongoing CPR per randomized woman (RR = 1.03, 95% CI: 0.87-1.21; P = 0.744, 300 women in each group), per cycle (RR = 1.01, 95% CI: 0.86-1.18; P = 0.934; 267 versus 259 cycles) and per oocyte utilized (RR = 1.02, 95% CI: 0.82-1.26; P = 0.873; 3286 versus 3185 oocytes) was reported. Findings were consistent with relevant cohort studies. Of the seven RCTs on embryo cryopreservation identified, three met the inclusion criteria (638 warming/thawing cycles at cleavage and blastocyst stage), none of which involved pronuclear-stage embryos. A higher CPR per cycle was noted with embryo vitrification compared with slow-freezing, though this was of borderline statistical significance (RR = 1.89, 95% CI: 1.00-3.59; P = 0.051; three RCTs; I2 = 71.9%). LBR per cycle was reported by one RCT performed with cleavage-stage embryos and was higher for vitrification (RR = 2.28; 95% CI: 1.17-4.44; P = 0.016; 216 cycles; one RCT). A secondary analysis was performed focusing on embryo cryosurvival rate. Pooled data from seven RCTs (3615 embryos) revealed a significant improvement in embryo cryosurvival following vitrification as compared with slow-freezing (RR = 1.59, 95% CI: 1.30-1.93; P < 0.001; I2 = 93%). WIDER IMPLICATIONS Data from available RCTs suggest that vitrification/warming is superior to slow-freezing/thawing with regard to clinical outcomes (low quality of the evidence) and cryosurvival rates (moderate quality of the evidence) for oocytes, cleavage-stage embryos and blastocysts. The results were confirmed by cohort studies. The improvements obtained with the introduction of vitrification have several important clinical implications in ART. Based on this evidence, in particular regarding cryosurvival rates, laboratories that continue to use slow-freezing should consider transitioning to the use of vitrification for cryopreservation.
476 citations
Cites background or methods from "An OHSS-Free Clinic by segmentation..."
...In this setting ovarian stimulation is optimized, including final oocyte maturation triggering with GnRH agonist in an antagonist cycle, all oocytes and/or embryos are cryopreserved (segment A) and later transferred to a receptive endometrium in a subsequent cycle (segment B) (Devroey et al., 2011)....
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...planned freeze all) (Devroey et al., 2011), 140 Rienzi et al....
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...The recent systematic application of cryopreservation for new indications such as cycle segmentation (i.e. planned freeze all) (Devroey et al., 2011), oocyte banking (Cobo et al., 2011a,2012) and pre-implantation genetic testing at the blastocyst stage (Schoolcraft et al., 2011) likely will…...
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...final oocyte maturation triggering with GnRH agonist in an antagonist cycle, all oocytes and/or embryos are cryopreserved (segment A) and later transferred to a receptive endometrium in a subsequent cycle (segment B) (Devroey et al., 2011)....
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TL;DR: Although fresh ET is the norm in IVF, results of this systematic review of observational studies suggest that pregnancies arising from the transfer of frozen thawed IVF embryos seem to have better obstetric and perinatal outcomes.
433 citations
TL;DR: A continuing expansion of both treatment numbers in Europe and more variability in treatment modalities resulting in a rising contribution to the birth rates in most participating countries is shown.
Abstract: Study question: What are the European trends and developments in ART and IUI in 2014 as compared to previous years?
Summary answer: The 18th ESHRE report on ART shows a continuing expansion of both treatment numbers in Europe and more variability in treatment modalities resulting in a rising contribution to the birth rates in most participating countries.
What is known already: Since 1997, ART data generated by national registries have been collected, analysed by the European IVF-monitoring (EIM) Consortium and reported in 17 manuscripts published in Human Reproduction.
Study design, size, duration: Continuous collection of European data by the EIM for ESHRE. The data for treatments performed in 2014 between 1 January and 31 December in 39 European countries were provided by national registries or on a voluntary basis by clinics or professional societies.
Participants/materials, setting, methods: From 39 countries and 1279 institutions offering ART services, a total of 776 556 treatment cycles, involving 146 148 with IVF, 362 285 with ICSI, 192 027 with frozen embryo replacement (FER), 15 894 with PGT, 56 516 with egg donation (ED), 292 with IVM and 3404 with frozen oocyte replacement (FOR) were reported. European data on IUI using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1364 institutions offering IUI in 26 countries and 21 countries, respectively. A total of 120 789 treatments with IUI-H and 49 163 treatments with IUI-D were included.
Main results and the role of chance: In 14 countries (17 in 2013), where all institutions contributed to their respective national registers, a total of 291 235 treatment cycles were performed in a population of ~208 million inhabitants, corresponding to 1925 cycles per million inhabitants (range: 423-2978 per million inhabitants). After treatment with IVF the clinical pregnancy rates (PR) per aspiration and per transfer were marginally higher in 2014 than in 2013, at 29.9 and 35.8% versus 29.6 and 34.5%, respectively. After treatment with ICSI the PR per aspiration and per transfer were also higher than those achieved in 2013 (28.4 and 35.0% versus 27.8 and 32.9%, respectively). After FER with own embryos the PR continued to rise, from 27.0% in 2013 to 27.6% in 2014. After ED a similar trend was observed with PR reaching 50.3% per fresh transfer (49.8% in 2013) and 48.7% for FOR (46.4% in 2013). The delivery rates (DR) after IUI remained stable at 8.5% after IUI-H (8.6% in 2013) and at 11.6% after IUI-D (11.1% in 2013). In IVF and ICSI together, 1, 2, 3 and ≥4 embryos were transferred in 34.9, 54.5, 9.9 and in 0.7% of all treatments, respectively (corresponding to 31.4%, 56.3, 11.5% and 1% in 2013). This evolution in embryo transfer strategy in both IVF and ICSI resulted in a singleton, twin and triplet DR of 82.5, 17.0 and 0.5%, respectively (compared to 82.0, 17.5 and 0.5%, respectively, in 2013). Treatments with FER in 2014 resulted in a twin and triplet DR of 12.4 and 0.3%, respectively (versus 12.5 and 0.3% in 2013). Twin and triplet DR after IUI were 9.5 and 0.3%, respectively, after IUI-H (in 2013:9.5 and 0.6%) and 7.7 and 0.3% after IUI-D (in 2013: 7.5 and 0.3%).
Limitation, reasons for caution: The method of data collection and reporting varies among European countries. The EIM receives aggregated data from various countries with variable levels of completeness. Registries from a number of countries have failed to provide adequate data about the number of initiated cycles and deliveries. As long as incomplete data are provided, the results should be interpreted with caution.
Wider implications of the findings: The 18th ESHRE report on ART shows a continuing expansion of treatment numbers in Europe. The number of treatments reported, the variability in treatment modalities and the rising contribution to the birth rates in most participating countries point towards the increasing impact of ART on reproduction in Europe. Being the largest data collection on ART, the report gives detailed information about ongoing developments in the field.
Study funding/competing interest(s): The study has no external funding and all costs are covered by ESHRE. There are no competing interests.
409 citations
TL;DR: Personalized IVF offers several benefits; it enables clinicians to give women more accurate information on their prognosis thus facilitating counselling especially in cases of extremes of ovarian response.
Abstract: Background The main objective of individualization of treatment in IVF is to offer every single woman the best treatment tailored to her own unique characteristics, thus maximizing the chances of pregnancy and eliminating the iatrogenic and avoidable risks resulting from ovarian stimulation. Personalization of treatment in IVF should be based on the prediction of ovarian response for every individual. The starting point is to identify if a woman is likely to have a normal, poor or a hyper response and choose the ideal treatment protocol tailored to this prediction. The objective of this review is to summarize the predictive ability of ovarian reserve markers, such as antral follicle count (AFC) and anti-Mullerian hormone (AMH), and the therapeutic strategies that have been proposed in IVF after this prediction. Methods A systematic review of the existing literature was performed by searching Medline, EMBASE, Cochrane library and Web of Science for publications in the English language related to AFC, AMH and their incorporation into controlled ovarian stimulation (COS) protocols in IVF. Literature available to May 2013 was included. Results The search generated 305 citations of which 41 and 25 studies, respectively, reporting the ability of AMH and AFC to predict response to COS were included in this review. The literature review demonstrated that AFC and AMH, the most sensitive markers of ovarian reserve identified to date, are ideal in planning personalized COS protocols. These sensitive markers permit prediction of the whole spectrum of ovarian response with reliable accuracy and clinicians may use either of the two markers as they can be considered interchangeable. Following the categorization of expected ovarian response to stimulation clinicians can adopt tailored therapeutic strategies for each patient. Current scientific trend suggests the elective use of the GnRH antagonist based regimen for hyper-responders, and probably also poor responders, as likely to be beneficial. The selection of the appropriate and individualized gonadotrophin dose is also of paramount importance for effective COS and subsequent IVF outcomes. Conclusion Personalized IVF offers several benefits; it enables clinicians to give women more accurate information on their prognosis thus facilitating counselling especially in cases of extremes of ovarian response. The deployment of therapeutic strategies based on selective use of GnRH analogues and the fine tuning of the gonadotrophin dose on the basis of potential ovarian response in every single woman can allow for a safer and more effective IVF practice.
407 citations
References
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TL;DR: The results suggest that vitrification using the Cryotop is the most efficient method for human oocyte cryopreservation.
Abstract: Two experiments were performed to develop a method to cryopreserve MII human oocytes. In the first experiment, three vitrification methods were compared using bovine MII oocytes with regard to their developmental competence after cryopreservation: (i) vitrification within 0.25-ml plastic straws followed by in-straw dilution after warming (ISD method); (ii) vitrification in open-pulled straws (OPS method); and (iii) vitrification in <0.1 microl medium droplet on the surface of a specially constructed fine polypropylene strip attached to a plastic handle (Cryotop method). In the second experiment, the Cryotop method, which had yielded the best results, was used to vitrify human oocytes. Out of 64 vitrified oocytes, 58 (91%) exhibited normal morphology after warming. After intracytoplasmic sperm injection, 52 became fertilized, and 32 (50%) developed to the blastocyst stage in vitro. Analysis by fluorescence in-situ hybridization of five blastocysts showed that all were normal diploid embryos. Twenty-nine embryo transfers with a mean number of 2.2 embryos per transfer on days 2 and 5 resulted in 12 initial pregnancies, seven healthy babies and three ongoing pregnancies. The results suggest that vitrification using the Cryotop is the most efficient method for human oocyte cryopreservation.
1,079 citations
"An OHSS-Free Clinic by segmentation..." refers background in this paper
...The excellent oocyte survival rates after oocyte vitrification justifies the use of oocyte cryopreservation as a routine approach (Kuwayama et al., 2005; Cobo et al., 2008; Nagy et al., 2009)....
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01 Jan 2007
902 citations
TL;DR: The Cryotop method preserves the potential of vitrified oocytes to fertilize and further develop, which is similar, when evaluated simultaneously, to fresh counterparts, indicating the possible use of this technology for egg donation programs, as well as a high potential for establishing oocyte banking.
486 citations
"An OHSS-Free Clinic by segmentation..." refers background in this paper
...The excellent oocyte survival rates after oocyte vitrification justifies the use of oocyte cryopreservation as a routine approach (Kuwayama et al., 2005; Cobo et al., 2008; Nagy et al., 2009)....
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TL;DR: This controlled-randomized, clinical trial confirmed the effectiveness of oocyte cryo-storage in an ovum donation programme, failing to demonstrate the superiority of using fresh oocytes with respect to the use of vitrified egg-banked ones in terms of OPR, but instead confirmed the non-inferiority of Vitrified oocytes.
Abstract: background: An efficient oocyte cryopreservation method is mandatory to establish a successful egg-banking programme. Although there are increasing reports showing good clinical outcomes after oocyte cryopreservation, there is still a lack of large controlled studies evaluating the effectiveness of oocyte cryo-banking. In this study, we aimed to compare the outcome of vitrified-banked oocytes with the gold standard procedure of employing fresh oocytes. methods: A randomized, prospective, triple-blind, single-centre, parallel-group controlled-clinical trial (NCT00785993), including 600 recipients (a ¼ 0.05 and power of 80% for sample-size calculation) selected among 1032 eligible patients from November 2008 to September 2009, was designed to compare the outcome of vitrified-banked oocytes with the gold standard procedure of employing fresh oocytes. The study was designed to establish the superiority of the ongoing pregnancy rate (OPR) of fresh oocytes over that of vitrified oocytes, by performing a likelihood ratio test in a logistic regression analysis expressed as odds ratio (OR) with 95% confidence interval (CI). A limit of 0.66 for OR of vitrified versus fresh groups was defined to set up a possible conversion from superiority to non-inferiority. Randomization was performed 1:1 based on a computer randomization list in vitrification (n ¼ 300) or fresh groups (n ¼ 300). The primary end-point was the OPR per randomized patient i.e. intention-to-treat population (ITT). Secondary end-points were clinical pregnancy (CPR), implantation (IR) and fertilization rates, respectively. Additionally, embryo developmental characteristics were recorded. results: There were no differences in donor ovarian stimulation parameters, demographic baseline characteristics for donors and recipients, ovum donation indications or male factor distribution between groups (NS). The OPR per ITT was 43.7 and 41.7% in the vitrification and fresh groups, respectively. The OR of OPR was 0.921 in favour of the vitrification group. Nevertheless, the 95% CI was 0.667–1.274, thus the superiority of fresh group with respect to OPR was not proven (P ¼ 0.744). Non-inferiority of the vitrified group compared with the fresh group was shown with a margin of 0.667, which was above the pre-established non-inferiority limit of 0.66. CPR per cycle (50.2 versus 49.8%; P ¼ 0.933) or per embryo-transfer (55.4 versus 55.6% ; P ¼ 0.974), and IR (39.9 versus 40.9%; P ¼ 0.745) were similar for patients receiving either vitrified or fresh oocytes. The proportion of top-quality embryos obtained either by inseminated oocyte (30.8 versus 30.8% for Day-2; and 36.1 versus 37.7% for Day-3, respectively) or by cleaved embryos (43.6 versus 43.8% for Day-2 and 58.4 versus 60.7% for Day-3, respectively) was similar between groups (NS). conclusions: This controlled-randomized, clinical trial confirmed the effectiveness of oocyte cryo-storage in an ovum donation programme, failing to demonstrate the superiority of using fresh oocytes with respect to the use of vitrified egg-banked ones in terms of OPR. Instead, the non-inferiority of vitrified oocytes was confirmed. These findings involve highly relevant issues that may open a new range of possibilities in ART. Clinical Trials identifier: www.clinicaltrials.gov: NCT 00785993.
455 citations