Assisted reproductive technology in Europe, 2011: results generated from European registers by ESHRE.

STUDY QUESTION: The 15th European IVF-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2011: are there any changes in the trends compared with previous years? SUMMARY ANSWER: Despite some fluctuations in the number of countries reporting data, while the overall number of ART cycles has continued to increase year by year, the pregnancy rates in 2011 decreased slightly to those reported in 2010, and the number of transfers with multiple embryos (3+) and the multiple delivery rates declined. WHAT IS KNOWN ALREADY: Since 1997, ART data in Europe have been collected and reported in 14 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, DURATION: Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE); cycles started between 1 January and 31 December 2011 are collected on a yearly basis. The data are collected by National Registers, when existing, or on a voluntary basis by personal information. PARTICIPANTS/MATERIALS SETTING, METHODS: From 33 countries (+2 compared with 2010), 1064 clinics reported 609 973 treatment cycles including: IVF 138 592, ICSI 298 918, frozen embryo replacement (FER) 129 693, egg donation (ED) 30 198, in vitro maturation 511, preimplantation genetic diagnosis/screening 6824 and frozen oocyte replacements 5237. European data on intrauterine insemination (IUI) using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 861 IUI laboratories in 24 countries. A total of 174 390 IUI-H and 41 151 IUI-D cycles were included. MAIN RESULTS AND THE ROLE OF CHANCE: In 17 countries where all clinics reported to the ART register, a total of 361 972 ART cycles were performed in a population of 285 million inhabitants, corresponding to 1269 cycles per million inhabitants. For all IVF cycles, the clinical pregnancy rates per aspiration and per transfer were stable with 29.1 and 33.2%, respectively, and for ICSI, the corresponding rates also were stable with 27.9 and 31.8%, respectively. In FER cycles, the pregnancy rate per thawing increased to 21.3% if compared with previous years. In ED cycles, the pregnancy rate per fresh transfer decreased to 45.8% (47.4% in 2010) and increased to 33.6% (33.3% in 2010) per thawed transfer. The delivery rate after IUI-H decreased to 8.3 (8.9 in 2010), and to 12.2% (13.8% in 2010) after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 27.5, 56.7, 14.5 and 1.3% of cycles, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (added together) were 80.8, 18.6 and 0.6%, respectively, resulting in a total multiple delivery rate of 19.2% compared with 20.6% in 2010, 20.2% in 2009, 21.7% in 2008, 22.3% in 2007 and 20.8% in 2006. In FER cycles, the multiple delivery rate was 13.2% (12.8% twins and 0.4% triplets). Twin and triplet delivery rates associated with IUI cycles were 9.7/0.6% and 7.3/0.3%, following IUI-H and IUI-D treatment, respectively. LIMITATIONS, REASONS FOR CAUTION: The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The 15th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than 600 000 cycles reported in 2011. Since 2006, the proportion of IVF to ICSI cycles has reached a plateau after a small decrease in 2009. Pregnancy and delivery rates after IVF remained relatively stable compared with 2010 and 2009. The pregnancy rate per aspiration in ICSI cycles declined for the first time by 0.9%. The multiple delivery rate is lower than ever before. STUDY FUNDING/COMPETING INTERESTS: The study had no external funding; all costs are covered by ESHRE. There are no competing interests.

Preserving fertility in women with endometrial cancer: two clinical cases.

Endometrial cancer is diagnosed increasingly in young women who wish to have children, and treatments intended to preserve fertility in these patients are becoming more common. The authors describe two women with endometrial cancer who were diagnosed and treated at our center and who needed assisted human reproductive technology, and review current knowledge based on similar cases.

Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHRE†.

STUDY QUESTION: The 14th European IVF--monitoring (EIM) report presents the results of medically assisted reproduction treatments including assisted reproductive technology (ART) cycles and intrauterine insemination (IUI) cycles initiated in Europe during 2010: are there changes in the trends compared with previous years? SUMMARY ANSWER: Despite some fluctuations in the number of countries reporting, the overall number of ART cycles has continued to increase year by year, and while pregnancy rates in 2010 remained similar to those reported in 2009, the number of transfers with multiple embryos (three or more) further declined. WHAT IS KNOWN ALREADY: Since 1997, ART data in Europe have been collected and reported in 13 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, DURATION: Retrospective collection of European ART data by the EIM Consortium for ESHRE; data were collected from cycles started between 1st January and 31st December 2010 by the National Registries of individual European countries, or on a voluntary basis by personal information for European countries without a national registry. PARTICIPANTS/MATERIALS SETTING, METHODS: Out of 31 countries, 991 clinics reported 550 296 ART treatment cycles: IVF (125 994), ICSI (272 771), frozen embryo replacement (FER, 114 593), egg donation (ED, 25 187), in vitro maturation (493), preimplantation genetic diagnosis/preimplantation genetic screening (6399) and frozen oocyte replacements (4859). European data on IUI using husband/partner's semen (IUI-H) or donor semen (IUI-D) were reported from 22 and 19 countries, respectively. A total of 176 512 IUI-H (+8.4% compared with 2009) and 38 124 IUI-D (+30.4% compared with 2009) cycles were included. MAIN RESULTS AND THE ROLE OF CHANCE: In 16 countries where all clinics reported to the national ART registry, a total of 267 120 ART cycles were performed in a population of 219 million inhabitants, corresponding to 1221 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer increased to 29.2 and 33.2%, respectively, and for ICSI, the corresponding rates also increased to 28.8 and 32.0%, when compared with the rates of 2009. In FER cycles, the pregnancy rate per thawing was 20.3%; in ED cycles the pregnancy rate per fresh transfer was 47.4% and per thawed transfer 33.3%. The delivery rate after IUI-H was 8.9 and 13.8% after IUI-D. In IVF and ICSI cycles, one, two, three and four or more embryos were transferred in 25.7, 56.7, 16.1 and 1.5%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 79.4, 19.6 and 1.0%, respectively, resulting in a total multiple delivery rate of 20.6% compared with 20.2% in 2009, 21.7% in 2008, 22.3% in 2007, 20.8% in 2006. In FER cycles, the multiple delivery rate was 12.8% (12.5% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 9.6/0.5 and 8.5/0.2%, following treatment with husband and donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION: The method of reporting is not standardized in Europe but varies among countries. Furthermore registries from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. Therefore, results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The 14th ESHRE report on ART and IUI treatments shows a continuing expansion of the number of ART treatment cycles in Europe, with more than half a million of cycles reported in 2010. The use of ICSI may have reached a plateau. When compared with 2009/2008, pregnancy and (multiple) delivery rates after IVF and ICSI remained relatively stable. The number of multiple embryo transfers (three or more embryos) has shown a decline. STUDY FUNDING/COMPETING INTERESTS: The study has no external funding; all costs are covered by ESHRE. There are no competing interests.

Adherence to reporting guidelines in observational studies concerning exposure to persistent organic pollutants and effects on semen parameters.

STUDY QUESTION: Are studies on semen quality in men exposed to persistent pesticides reported according to the 'strengthening the reporting of observational studies in epidemiology' (STROBE) recommendations and the guidelines for the appraisal of semen quality studies (SEMQUA)? SUMMARY ANSWER: Most studies of the impact of pesticides on semen quality do not follow the STROBE and SEMQUA guidelines, thus adherence is low, especially in methodological aspects. WHAT IS KNOWN ALREADY: Much of the controversy about reduced semen quality in recent decades arises from a lack of standardization in the methodology applied, despite the existence of several validated instruments for evaluating the quality of reporting. Indeed, SEMQUA was purpose-designed for the particular characteristics of semen quality studies. STUDY DESIGN, SIZE, DURATION: A structured literature search identified eligible articles reporting on persistent pesticides and human semen quality, published in English before 1 September 2012. Opinion articles and reviews were excluded. We assessed the adherence to reporting guidelines of the articles, using and comparing the STROBE statement and the SEMQUA guidelines, in both cases with indicators relevant to observational studies of semen quality. PARTICIPANTS/MATERIALS, SETTING, METHODS: A comprehensive bibliographic search in various electronic literature databases using the key words 'sperm' and 'pesticide' obtained 1179 papers, of which 46 were valid for our purposes. The papers examined occupational (26) and environmental exposure (20). Two of the present authors independently piloted the data extraction form for this review. The articles were then evaluated by two researchers using the STROBE and SEMQUA checklists. MAIN RESULTS AND THE ROLE OF CHANGE: Although no significant differences were found between the overall degree of compliance with STROBE and SEMQUA (47.0 ± 18.5% versus 43.1 ± 11.6%), there were significant differences when only methodological aspects were considered (48.4 ± 21.0% versus 39.5 ± 17.4%; P < 0.001). We observed an increase over time in the degree of compliance, for SEMQUA (r = 0.61 and P < 0.001) and STROBE (r = 0.45 and P < 0.01). The papers that reported a negative effect of exposure to persistent pesticides on sperm concentration presented a lower level of compliance to SEMQUA (42.1 ± 18.3% versus 57.6 ± 14.2%; P < 0.01) and STROBE (40.2 ± 10.3% versus 49.5 ± 11.6%; P < 0.05) than those which recorded no such influence. The year of publication and the observed effect on sperm concentration were the only candidate variables included in the model of stepwise multiple regression model for the 'degree of compliance' variables of SEMQUA and STROBE. LIMITATIONS, REASONS FOR CAUTION: Other characteristics of reporting quality, such as legibility, were not evaluated. WIDER IMPLICATIONS OF THE FINDINGS: The low degree of compliance observed is consistent with that observed in other studies of reproductive medicine and highlights the need to improve the design of studies of semen quality. SEMQUA proved to be a more specific tool than STROBE for the field of semen quality. Editors, reviewers and authors should be aware of SEMQUA and apply it when assessing papers on semen quality. STUDY FUNDING/COMPETING INTEREST(S): No research funding was received and none of the authors have any conflict of interests.

Embryologists' health: a nationwide online questionnaire.

PURPOSE: The present study evaluates health status and its relation with occupational characteristics and with burnout syndrome among embryologists. METHODS: A cross-sectional design was used to conduct an online self-assessment survey, sent to all members of the Spanish Association of Clinical Embryologists. The questionnaire contained occupational questions and two standard instruments: 'Short Form-12 Health Survey' as a measure of physical (PCS-12) and mental (MCS-12) health and the Maslach Burnout Inventory-General Survey (MBI-GS) to evaluate the degree of burnout. RESULTS: The PCS-12 obtained for the Spanish embryologists was higher than that for the reference population. However, the total MCS-12 was significantly lower than that observed in non-institutionalised males and females representative of the general Spanish population aged 35-44 years. In the linear regression model, the dependent variable PCS-12 was related indirectly with the variables number of hours worked per week, BMI, back pain, leg pain and visual discomfort. In the linear regression model, the dependent variable MCS-12 was indirectly related to the gender (male reference; female coefficient regression: -3.23), exhaustion and cynicism dimensions of the MBI-GS. A total of 87 (36.3%) embryologists presented a high score on at least one of the MBI-GS dimensions. CONCLUSION: In this sample of Spanish embryologists, a norm measure (SF-12) showed their physical health to be better than the average for the general population, but that their mental health was poorer. A significant indirect relation was observed between mental health and burnout syndrome. Strategies to reduce occupational stress and problems should form part of the training provided for clinical embryologists.

Assisted reproductive technology in Europe, 2009: results generated from European registers by ESHRE.

STUDY QUESTION: The 13th European in vitro fertilization (IVF)-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2009: are there any changes in the trends compared with previous years? SUMMARY ANSWER: Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year and, while pregnancy rates in 2009 remained similar to those reported in 2008, the number of transfers with multiple embryos (3+) and the multiple delivery rates declined. WHAT IS KNOWN ALREADY: Since 1997, ART data in Europe have been collected and reported in 12 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, DURATION: Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE); cycles started between 1st January and 31st December are collected on a yearly basis; the data are collected by the National Registers, when existing, or on a voluntary basis. PARTICIPANTS/MATERIALS SETTING, METHODS: From 34 countries (-2 compared with 2008), 1005 clinics reported 537 463 treatment cycles including: IVF (135 621), intracytoplasmic sperm injection (ICSI, 266 084), frozen embryo replacement (FER, 104 153), egg donation (ED, 21 604), in vitro maturation (IVM, 1334), preimplantation genetic diagnosis/screening (PGD/PGS, 4389) and frozen oocyte replacements (FOR, 4278). European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor (IUI-D) semen were reported from 21 and 18 countries, respectively. A total of 162 843 IUI-H (+12.7%) and 29 235 IUI-D (+17.3%) cycles were included. Data available from each country are presented in the tables; total values (as numbers and percentages) refer to those countries where all data have been reported. MAIN RESULTS AND THE ROLE OF CHANCE: In 21 countries where all clinics reported to the ART register, a total of 399 020 ART cycles were performed in a population of 373.8 million, corresponding to 1067 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.9 and 32.9%, respectively and for ICSI, the corresponding rates were 28.7 and 32.0%. In FER cycles, the pregnancy rate per thawing was 20.9%; in ED cycles, the pregnancy rate per transfer was 42.3%. The delivery rate after IUI-H was 8.3 and 13.4% after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 24.2, 57.7, 16.9 and 1.2%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 79.8, 19.4 and 0.8%, respectively, resulting in a total multiple delivery rate of 20.2%, compared with 21.7% in 2008, 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.0% (12.7% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 10.4/0.7% and 10.3/0.5%, following treatment with husband and donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION: The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The 13th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than half a million of cycles reported in 2009. The use of ICSI has reached a plateau. Pregnancy and delivery rates after IVF and ICSI remained relatively stable compared with 2008 and 2007. The number of multiple embryo transfers (3+ embryos) and the multiple delivery rate have shown a clear decline.

Proposal of guidelines for the appraisal of SEMen QUAlity studies (SEMQUA).

STUDY QUESTION: Is there a need for a specific guide addressing studies of seminal quality? SUMMARY ANSWER: The proposed guidelines for the appraisal of SEMinal QUAlity studies (SEMQUA) reflect the need for improvement in methodology and research on semen quality. WHAT IS KNOWN ALREADY: From an examination of other instruments used to assess the quality of diagnostic studies, there was no guideline on studies of seminal quality. STUDY DESIGN, SIZE AND DURATION: Through systematic bibliographic search, potential items were identified and grouped into four blocks: participants, analytical methods, statistical methods and results. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Our findings were presented to a panel of experts who were asked to identify opportunities for improvement. Then, a checklist was designed containing the questions generated by the items that summarize the essential points that need to be considered for the successful outcome of a SEMQUA. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen items were identified, from which 19 questions, grouped into four blocks, were generated to constitute the final checklist. An explanation for the inclusion of each item was provided and some examples found in the bibliographic search were cited. LIMITATIONS AND REASONS FOR CAUTION: We consider that not all items are equally applicable to all study designs, and so the hypothetical results are not comparable. For that reason, a score would not be fair to critically appraise a study. This checklist is presented as an instrument for appraising SEMQUAs and therefore remains open to constructive criticism. It will be further developed in the future, in parallel with the continuing evolution of SEMQUAs. WIDER IMPLICATIONS OF THE FINDINGS: The final configuration of the SEMQUA is in the form of a checklist, and includes the items generally considered to be essential for the proper development of a SEMQUA. The final checklist produced has various areas of application; for example, it would be useful for designing and constructing a SEMQUA, for reviewing a paper on the question, for educational purposes or as an instrument for appraising the quality of research articles in this field. STUDY FUNDING/COMPETING INTEREST(S): None.

Assisted reproductive technology in Europe, 2007: results generated from European registers by ESHRE.

BACKGROUND: This 11th European IVF-monitoring report presents the results of assisted reproductive technology (ART) treatments initiated in Europe during 2007. METHODS: From 33 countries, 1029 clinics reported 493 184 treatment cycles: IVF (120 761), ICSI (256 642), frozen embryo replacement (91 145), egg donation (15 731), preimplantation genetic diagnosis/preimplantation genetic screening (4638), in vitro maturation (660) and frozen oocytes replacements (3607). Overall, this represents a 7.6% increase since 2006, mostly related to an increase in all registers. IUI using husband/partner's (IUI-H) and donor (IUI-D) semen was reported from 23 countries: 142 609 IUI-H (+6.2%) and 26 088 IUI-D (+7.2%). RESULTS: In 18 countries where all clinics reported, 376 971 ART cycles were performed in a population of 425.6 million (886 cycles per million). The clinical pregnancy rates per aspiration and per transfer were 29.1 and 32.8% for IVF, and 28.6 and 33.0% for ICSI. Delivery rate after IUI-H was 10.2% in women aged < 40 years. In IVF/ICSI cycles, 1, 2, 3 and ≥4 embryos were transferred in 21.4, 53.4, 22.7 and 2.5% of cycles, with no decline in the number of embryos per transfer since 2006. The proportion of multiple deliveries (22.3: 21.3% twin and 1.0% triplet), did not decrease compared with 2006 (20.8%) and 2005 (21.8%). In women < 40 years undergoing IUI-H, twin deliveries occurred in 11.7% and triplets in 0.5%. CONCLUSIONS: In comparison with previous years, the reported number of ART cycles in Europe increased in 2007; pregnancy rates increased marginally, but the earlier decline in the number of embryos transferred and multiple births did not continue.

Assisted reproductive technology in Europe, 2008: results generated from European registers by ESHRE.

BACKGROUND: This 12th European IVF-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2008. METHODS: From 36 countries (3 more compared with 2007), 1051 clinics reported 532 260 treatment cycles including: IVF (124 539), ICSI (280 552), frozen embryo replacements (FER, 97 120), egg donation (ED, 13 609), in vitro maturation (IVM, 562), preimplantation genetic diagnosis/screening (PGD/PGS, 2875) and frozen oocyte replacements (FOR, 4080). Overall, this represents a 7.9% increase in the activity since 2007, which is mainly related to an increase in cycles from almost all registers and only partially to the new countries entering EIM (Estonia, Kazakhstan, Moldova and Romania, 5480 cycles in total). European data on intrauterine insemination using husband/partner's (IUI-H) and donor (IUI-D) semen were reported from 27 and 21 countries, respectively. A total of 144 509 IUI-H (+1.5%) and 24 960 IUI-D (-4.3%) cycles were included. RESULTS: In 19 countries where all clinics reported to the ART register, a total of 350 143 ART cycles were performed in a population of 369.8 million, corresponding to 947 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.5 and 32.5%, respectively, and for ICSI the corresponding rates were 28.7 and 31.9%. In FER cycles, the pregnancy rate per thawing was 19.3%. The delivery rate after IUI was 9.1% for IUI-H and 13.8% for IUI-D. In IVF and ICSI cycles, one, two, three and four or more embryos were transferred in 22.4, 53.2, 22.3 and 2.1%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 78.3, 20.7 and 1.0%, respectively, resulting in a total multiple delivery rate of 21.7%, compared with 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.7% (13.4% twins and 0.3% triplets). In women undergoing IUI, twin and triplet deliveries occurred in 10.6% and 0.7% with IUI-H and in 9.4 and 0.3% with IUI-D, respectively. CONCLUSIONS: In comparison with previous years, there was an increase in the reported number of ART cycles in Europe. For the first time in 5 years, the pregnancy rates failed to show a year-on-year increase. Compared with 2007, the number of transfers of multiple embryos (3+) and a multiple delivery rate showed a marginal decline.

Acceptable variability in external quality assessment programmes for basic semen analysis.

BACKGROUND: External quality assessment is essential in modern andrology laboratories. To assess the proficiency of laboratories participating in an external quality assessment programme (EQAP), limits for acceptable variability must be determined. Limits currently specified largely depend on criteria set by the organizers of individual EQAP schemes. The objective of this study was to evaluate the different criteria described in ISO 13528: 2005 for calculating acceptable variability in EQAP when applied to basic semen analysis parameters. METHODS AND RESULTS: The data used in this study were the means and standard deviations obtained for independent samples from two EQAPs, one national (Spanish) and one international (European). The acceptable variability according to ISO 13528: 2005 was calculated using four types of criteria: (i) ± 3 standard deviations of the results of all participating laboratories; (ii) ± 3 standard deviations of the results of expert laboratories; (iii) quality specifications based on biological variability, state-of-the-art and clinicians' opinions and (iv) the same quality specifications adjusted for the uncertainty of the assigned value. The first two strategies resulted in very wide ranges of acceptable variability. Conversely, the strategy based only on quality specifications resulted in very narrow ranges. For the fourth strategy, acceptable ranges were intermediate between the results produced with the other strategies. The third and fourth strategies did not produce observable differences in acceptable ranges when the model used for calculating the specifications of analytical quality was changed. CONCLUSIONS: It is essential that EQAPs for semen parameters should determine the ranges for acceptable variability in results. Moreover, these ranges must be clinically useful, i.e. the variability should have a minimal negative impact on clinical decisions. The exact definition of 'expert laboratory' is more important than the model chosen for estimating analytical quality specifications in an EQAP for semen parameters in basic semen analysis.

Comparison of IVF cycles reported in a voluntary ART registry with a mandatory registry in Spain.

BACKGROUND: Monitoring assisted reproductive technology (ART) is essential to evaluate the performance of fertility treatment and its impact on birth rates. In Europe, there are two kinds of ART registers: voluntary and mandatory. The validity of register data is very important with respect to the quality of register-based observational studies. The aim of this paper is to determine the degree of agreement between voluntary and mandatory ART registers. METHODS: The two sources for the data compared in this study (referring to 2005 and 2006) were FIVCAT.NET (an official compulsory Assisted Reproduction Registry within the Health Ministry of the Regional Government of Catalonia, to which all authorized clinics, both public and private, performing assisted reproduction in the region are obliged to report) and the register of the Spanish Fertility Society (SEF), to which data are provided on a voluntary basis. The SEF register data were divided into two groups: (i) data from clinics in Catalonia (SEF-CAT); (ii) data from the rest of Spain, excluding Catalonia (SEF-wCAT). The techniques compared were IVF cycle using patients' own eggs (IVF cycle) versus donor egg cycles. RESULTS: For IVF cycles, the voluntary ART register reflected 77.2% of those on the official one, but the corresponding figure was only 34.4% with respect to donated eggs. The variables analysed in the IVF cycle (insemination technique used, patients' age, number of embryos transferred, pregnancy rates, multiple pregnancies and deliveries) were similar in the three groups studied. However, we observed significant differences in donor egg cycles with regard to the insemination technique used, pregnancy rates and multiple pregnancies between the voluntary and the official register. CONCLUSIONS: Data from the voluntary ART register for IVF cycles are valid, but those for donor egg cycles are not. Further study is necessary to determine the reasons for this difference.

Assisted reproductive technology in Europe, 2006: results generated from European registers by ESHRE.

BACKGROUND: In this 10th European IVF-monitoring (EIM) report, the results of assisted reproductive techniques from treatments initiated in Europe during 2006 are presented. Data were mainly collected from existing national registers. METHODS: From 32 countries, 998 clinics reported 458 759 treatment cycles including: IVF (117 318), ICSI (232 844), frozen embryo replacement (FER, 86 059), egg donation (ED, 12 685), preimplantation genetic diagnosis/screening (6561), in vitro maturation (247) and frozen oocytes replacements (3498). Overall this represents a 9.7% increase in activity since 2005, which is partly due to an increase in registers (seven more countries with complete coverage). European data on intrauterine insemination using husband/partner's (IUI-H) and donor (IUI-D) semen were reported from 22 countries. A total of 134 261 IUI-H and 24 339 IUI-D cycles were included. RESULTS: In 20 countries, where all clinics reported to the IVF register, a total of 359 110 assisted reproductive technology (ART) cycles were performed in a population of 422.5 million, corresponding to 850 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 29.0 and 32.4%, respectively. For ICSI, the corresponding rates were 29.9 and 33.0%. After IUI-H the delivery rate was 9.2% in women below 40. After IVF and ICSI the distribution of transfer of one, two, three and four or more embryos was 22.1, 57.3, 19.0 and 1.6%, respectively. Compared with 2005, fewer embryos were replaced per transfer, but significant national differences in practice were apparent. The proportion of singleton, twin and triplet deliveries after IVF and ICSI combined was 79.2, 19.9 and 0.9%, respectively. This gives a total multiple delivery rates of 20.8% compared with 21.8% in 2005 and 22.7% in 2004. IUI-H in women below 40 years of age resulted in 10.6% twin and 0.6% triplet pregnancies. CONCLUSIONS: Compared with previous years, the reported number of ART cycles in Europe has increased, pregnancy rates have increased marginally, even though fewer embryos were transferred and the multiple delivery rates have declined.

Impact of the Spanish Fertility Society guidelines on the number of embryos to transfer.

The multiple pregnancy rate in assisted reproduction treatment cycles depends, fundamentally, on the number of embryos transferred. It is essential that patients and professionals should have good practical guidelines on the best number of embryos to be transferred in each cycle in order to obtain high pregnancy rates with minimal risk of multiple pregnancies. This study analysed the impact made by the Spanish Fertility Society (SEF) guidelines on the number of embryos to be transferred, as regards the policies adopted at clinics in Spain and the resulting financial repercussions. Data were collected from the assisted reproduction treatment register of the SEF and compared over three periods of time: 2002-2003, with no legal regulation and no SEF guidelines; 2004, with only legal regulation; and 2005-2006, with legal regulation and SEF guidelines. The acceptance of SEF guidelines varies according to the IVF technique. The guidelines have led to a reduction in multiple pregnancy rates, especially concerning triplets, in patients' own-egg and with donor-egg cycles. Even without full implantation, these results validate the clinical utility of the SEF guidelines. They constitute a useful tool to reduce the incidence of the principal adverse effect of treatment cycles: multiple pregnancies. The multiple pregnancy rate in assisted reproduction cycles depends fundamentally on the number of embryos transferred. It is essential that patients and professionals should have good practical guidelines on the best number of embryos to be transferred in each cycle in order to obtain high pregnancy rates with minimal risk of multiple pregnancies. The purpose of this study was to analyse the impact made by the Spanish Fertility Society (SEF) guidelines on the number of embryos to be transferred, as regards the policies adopted at clinics in Spain, and the resulting financial repercussions. Data were collected from the assisted reproduction register of the SEF and compared over three periods of time: 2002-2003, when there was no legal regulation and no SEF guidelines; 2004, when there was only legal regulation; and 2005-2006, when there was legal regulation and SEF guidelines. The degree of acceptance of SEF guidelines varies according to the IVF technique employed. The guidelines have led to a reduction in multiple pregnancy rates, especially concerning triplets, using patients' own eggs and with donor eggs. The reduction in the financial cost of deliveries achieved in the years 2005-2006 ranged from 890,187 to 18,593,242 euros, and the incremental cost per percentage point of multiple pregnancy avoided is 2,989,613 euros. In conclusion, even without full implementation, these results validate the clinical utility of the SEF guidelines. They constitute a useful tool to reduce the incidence of the principal adverse effect of assisted reproduction cycles, namely multiple pregnancies.

Sperm chromatin structure assay and classical semen parameters: systematic review.

The present study is based on a PubMed search and compares the clinical validity of classical semen parameters (CSP) and the sperm chromatin structure assay (SCSA) in different clinical contexts. The PubMed database was searched using keywords on the sperm diagnostic test for pregnancy in three clinical scenarios: (i) couples attempting to conceive; (ii) couples who had been attempting to conceive for 12months without success; and (iii) couples treated with intrauterine insemination (IUI). There was a considerable heterogeneity among the studies included. For couples attempting to conceive following a SCSA that produced an abnormal result, the likelihood of male factor infertility ranged from a pre-test value of 7.5% to a post-test value of 32.1% [95% confidence interval (CI) 15.7-54.5], while after CSP with an abnormal result, the post-test probability was 17.3% (95% CI 11.8-24.5). For a pre-test prevalence of male factor infertility of 50%, the post-test probability of male factor infertility after an abnormal test is very similar for both SCSA and CSP. In couples treated with IUI, the clinical validity of SCSA is higher than that of sperm morphology alone, but not enough to introduce SCSA as a test in male infertility work-up.

Comparison of methods to determine the assigned value in an external quality control programme for embryo evaluation.

This study set out to establish adequate assigned values for a National External Quality Control Programme of embryo evaluation. The results obtained by Spanish laboratories in this programme are compared with those of a group of national experts in embryo quality. Image-based embryo evaluation consists not only of classifying embryos as being of optimal, moderate or poor quality, but also of specifying the clinical decision to be taken regarding each embryo (transfer, cryopreservation or rejection). The proportion of embryos for which there was a high degree of agreement among the experts was 98.3% for embryo classification and 93.3% for clinical decision; for the laboratories, the respective values were 44.2 and 42.5%. With respect to the interobserver agreement among laboratories and experts, kappa coefficients were lower than 0.6 both for classification and for clinical decision. The experts recommended cryopreservation of a higher percentage of embryos classified as poor quality than did the laboratories (28 versus 4%, P = 0.05). The data obtained show that the agreement among laboratories is lower than among experts, and that the concordance among experts and laboratories is moderate. Therefore, it is recommended that an assigned value from external quality control programmes is established based on the consensus values obtained from experts.

Assisted reproductive technologies in public and private clinics.

The aim of this study was to analyse the influence of the type of service provided by assisted reproduction clinics. The activities, treatment patterns and results achieved by assisted reproduction centres in Spain were examined, comparing public and private clinics. A retrospective study was carried out using the Assisted Reproductive Technology Register of the Spanish Fertility Society for 2002-2004. The results showed that 74%, 96% and 99% of IVF/intracytoplasmic sperm injection, oocyte donation and preimplantation genetic diagnosis cycles, respectively, were carried out in the private sector. Public clinics performed proportionally more transfers of three embryos than the private clinics (48.1% versus 41.7%). More elective transfers were performed in private clinics. Pregnancy rates per cycle started, per puncture and per transfer were significantly higher among private than public clinics (29.1%, 32.7% and 35.9% versus 25.2%, 28.5% and 32.6%, respectively) (P < 0.05). Implantation rate has risen year on year in both types of clinic and was significantly higher (P < 0.05), every year, among the private clinics. The multiple-pregnancy rate was significantly higher among the private clinics (30.8% versus 26.4%) (P < 0.05). In conclusion, differences exist between public and private clinics as regards to their volume of activity, the range of services offered, clinical practice and results achieved.

Thyroid hormones in fibrocystic breast disease.

This study was undertaken to evaluate the role of thyroid hormones in fibrocystic breast disease. The concentrations of thyroid-stimulating hormone (TSH), thyroxine (T4), free T4 and free triiodothyronine (T3) were determined in serum of 50 women with fibrocystic breast disease without macrocysts (cysts of over 3 mm diameter) and in the serum and breast cyst fluid (BCF) of 60 women with fibrocystic breast disease and macrocysts. Possible relationships between thyroid hormones and estradiol, dehydroepiandrosterone sulfate, testosterone, progesterone and 17-hydroxyprogesterone in the BCF also were analyzed. Serum thyroid hormone levels did not differ between the two groups. Free T3 levels were higher in BCF than in serum (p < 0.001), whereas T4, free T4 and TSH concentrations were lower in BCF as compared to serum (p < 0.001). Cysts were divided according to their K+/Na+ ratio because a ratio above 3 represents a predictor of malignant transformation. Free T3 concentrations were higher in BCF than in serum, in both low K+/Na+ cysts and in cysts with a K+/Na+ ratio above 3; those cysts with a high K+/Na+ ratio had the highest free T3 concentration. Free T3 in cysts correlated positively to the K+/Na+ ratio (r = 0.831; p < 0.001). Multiple linear regression analysis demonstrated that the concentration of free T3 in BCF was predicted statistically by the positive regression coefficient for the estradiol concentration. No candidate variable was included in the model to predict concentrations of TSH, free T4 or T4 in BCF. These data suggest an important role of free T3 in the physiology of fibrocystic breast disease.

Decreased levels of circulating CD4+ T lymphocytes during normal human pregnancy.

Peripheral blood mononuclear cell (PBMC) populations during human pregnancy have been investigated by many authors, although the different results obtained, principally in relation to T cells, are very discrepant. In this study we aimed to exclude all the possible causes of these discrepancies: small sample size; diurnal rhythm of CD4+ T cells; smoking habits; haemodilution which occurs during pregnancy and inappropriate statistical analysis; in order to determine whether gestation has a definite effect on PBMC populations. We found that the percentage of CD4+ T lymphocytes decreases in the first and second trimesters, returns to the non-pregnant level in the third trimester and remains there in the postpartum period. The percentages of CD3+ T lymphocytes run parallel to those of CD4+ while CD8+ T lymphocytes do not vary. The proportion of CD16+ cells, which include mature NK cells, diminishes in the second trimester and this reduction is maintained in the third trimester and the puerperium. No variation was found in the other PBMC studied (CD20+ lymphocytes, CD14+ monocytes and D/DR+ cells). When parity was considered no difference was seen between primiparous and multiparous women in any of the cell populations tested.

Short-lived suppressor cell activity during normal human pregnancy.

Short-lived suppressor cell (SLSC) activity was determined in normal pregnant women. This activity was significantly increased in all three trimesters of pregnancy and during the first week postpartum. When pregnant women were divided into primiparous and multiparous groups, no significant differences were found between the two groups in any of the periods studied. These results suggest that increased SLSC activity may play a role in the materno-fetal tolerance and that parity has no influence on this activity.

Diagnosis of pelvic inflammatory disease with 99mtechnetium-hexamethylpropylenamine-oxime-labeled autologous leukocytes and pelvic radionuclide scintigraphy.

In a prospective study, we assessed the performance of pelvic radionuclide scintigraphy after the injection of 99mtechnetium-hexamethylpropylenamine-oxime-labeled autologous leukocytes as a noninvasive tool for the differential diagnosis of pelvic inflammatory disease (PID). The results of radionuclide scintigraphy in 20 women with PID confirmed laparoscopically were compared with the findings in 20 others hospitalized for suspected PID but with PID ruled out later by laparoscopy. The proportion of radionuclide scintigraphic findings demonstrating increased uptake in the genital region, compatible with an inflammatory process, was significantly larger (P < .001) in patients with PID (95%) than in those without PID (15%). The sensitivity of the technique was 95% and specificity was 85%; in all, 90% of the patients were correctly classified. We conclude that radionuclide scintigraphy preceded by the injection of 99mtechnetium-hexamethylpropylenamine-oxime-labeled autologous leukocytes can detect PID in a high proportion of patients.