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Study Question: What was the performance of different pretreatment prediction models for IVF, which were developed based on UK/US population (McLernon 2016 model, Luke model, Dhillon model, and McLernon 2022 model), in wider populations?, Summary Answer: For a patient in China, the published pretreatment prediction models based on the UK/US population provide similar discriminatory power with reasonable AUCs and underestimated predictions., What Is Known Already: Several pretreatment prediction models for IVF allow patients and clinicians to estimate the cumulative probability of live birth in a cycle before the treatment, but they are mostly based on the population of Europe or the USA, and their performance and applicability in the countries and regions beyond these regions are largely unknown., Study Design, Size, Duration: A total of 26 382 Chinese patients underwent oocyte pick-up cycles between January 2013 and December 2020., Participants/materials, Setting, Methods: UK/US model performance was externally validated according to the coefficients and intercepts they provided. Centre-specific models were established with XGboost, Lasso, and generalized linear model algorithms. Discriminatory power and calibration of the models were compared as the forms of the AUC of the Receiver Operator Characteristic and calibration curves., Main Results and the Role of Chance: The AUCs for McLernon 2016 model, Luke model, Dhillon model, and McLernon 2022 model were 0.69 (95% CI 0.68-0.69), 0.67 (95% CI 0.67-0.68), 0.69 (95% CI 0.68-0.69), and 0.67 (95% CI 0.67-0.68), respectively. The centre-specific yielded an AUC of 0.71 (95% CI 0.71-0.72) with key predictors including age, duration of infertility, and endocrine parameters. All external models suggested underestimation. Among the external models, the rescaled McLernon 2022 model demonstrated the best calibration (Slope 1.12, intercept 0.06)., Limitations, Reasons for Caution: The study is limited by its single-centre design and may not be representative elsewhere. Only per-complete cycle validation was carried out to provide a similar framework to compare different models in the sample population. Newer predictors, such as AMH, were not used., Wider Implications of the Findings: Existing pretreatment prediction models for IVF may be used to provide useful discriminatory power in populations different from those on which they were developed. However, models based on newer more relevant datasets may provide better calibrations., Study Funding/competing Interest(s): This work was supported by the National Natural Science Foundation of China [grant number 22176159], the Xiamen Medical Advantage Subspecialty Construction Project [grant number 2018296], and the Special Fund for Clinical and Scientific Research of Chinese Medical Association [grant number 18010360765]., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: Many studies in the literature have found an association between geographic origin and poorer IVF outcomes in African American and Asian minority populations compared with Caucasian populations. The limitations of these studies are multiple (inconsistencies in the characterization of ethnic groups, mostly multicenter studies with large variability in success rates between centers, minorities having more limited and delayed access to care). Thus, socioeconomic status may have been an important bias in judging environmental or "genetic" factors. The objective of our study is to determine whether geographic origin would influence IVF response and outcomes in a French university hospital center with equal access to care., Material and Methods: This was a retrospective single-center observational study from January 2013 to January 2020 comparing IVF response in 3 populations of similar size at our Medically Assisted Reproduction center, with all charges covered by Medicare. The primary objective was ovarian response to IVF, and the secondary objectives were clinical pregnancy rate and live birth rate per cycle started., Results: We analyzed 1669 cycles of first IVF attempt in women from Europe (525), Sub-Saharan Africa (649) and Maghreb (495). The SSA and Maghrebi women had a higher BMI. SSA women were more often affected by tubal or uterine infertility, HIV or HBV infection, and were less often nulliparous. The indication of male infertility was more frequent in Maghrebi women with a higher ICSI rate. There was no significant difference in the duration of stimulation, endometrial thickness at induction, number of oocytes collected, fertilization rate, number of embryos transferred and frozen. Nevertheless, the cancellation rate was higher in SSA and Maghrebi women and the total dose of gonadotropins was higher in SSA. No significant difference was found between Maghrebi and European women on IVF outcomes except for a lower number of total embryos in Maghrebi women (3.33 vs. 4.13 on average, P<0.001). The SSA had a lower rate of mature oocytes per puncture (66 % vs. 73 %, P<0.001), a lower number of total embryos per puncture (3.56 vs. 4.13 on average, P<0.016), a lower rate of clinical pregnancies per cycle (11.7% vs. 20.4%, P<0.001), a lower rate of live births per cycle (6.9% vs. 15.2%, P<0.001)., Conclusion: There was no significant difference between European and Maghrebi women at the end of IVF, but the results were lower for those from SSA., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Introduction : To study the impact of biosimilars in assisted reproductive treatments, we performed a review of the literature. Biosimilars are a bioequivalent chemical drug referred to the original. Their production is strongly requested in order to reduce drug cost and reduce health economic impact on national health system. In assisted reproductive treatments different gonadotropin biosimilars are being produced. Areas covered : For this reason, we performed a review of the literature on follitropin alfa Gonal-F biosimilar, Ovaleap and Bemfola, to assess their cost efficacy in national health system. Cost effective (CE) analysis and incremental cost-effectiveness ratio (ICER) were used as parameters for biosimilar impact evaluation in the national health system economy. In particular, they had only slight impact on cost reduction of recombinant follitropin alfa products in Europe. Expert opinion : considering cost-effective analysis, Gonal-F remains the first choice for national health systems. However, well-designed powered methods are strongly needed to assess biosimilars cost-effectiveness.

Purpose: To evaluate whether ICSI offers any benefit compared with IVF in different ovarian response categories in case of non-male factor infertility., Methods: This is a retrospective multicenter analysis using individual patient data, conducted in 15 tertiary referral hospitals in Europe (1 center in Belgium and 14 in Spain). The study included the first cycle of all patients undergoing ovarian stimulation for IVF or ICSI in a GnRH antagonist protocol. Only patients having either IVF or ICSI for non-male factor infertility were included. Patients were divided into 4 groups based on their ovarian response as follows: group A, poor responders (1-3 oocytes); group B, suboptimal responders (4-9 oocytes); group C, normal responders (10-15 oocytes); group D, high responders (> 15 oocytes)., Results: In total, 4891 patients were analyzed, of whom 4227 underwent ICSI and 664 IVF. There was no significant difference for the insemination method (ICSI vs. IVF) used among the different ovarian response categories: 87% vs. 13%, 87% vs. 13%, 86% vs. 14%, 84% vs. 16%, for groups A, B, C, and D, respectively, p value = 0.35. Mean fertilization rates and embryo utilization rates were comparable between IVF and ICSI in the whole cohort. Fresh and cumulative LBR did not differ significantly for IVF and ICSI in poor, suboptimal, normal, and high responders., Conclusion: There is no advantage of ICSI over IVF as insemination method for non-male factor infertility, irrespective of the ovarian response. The number of oocytes retrieved has no value for the selection of the insemination procedure in case of non-male infertility.

The mediocre outcome of microsurgery results in patients with extensive tubal disease was the original driving force behind the search for new methods to assist these infertile patients. Many unsuccessful attempts were carried out before the birth of the first in vitro fertilization baby in Europe 40 years ago. Many pioneers worked tirelessly to develop the tools, procedures, and research necessary. Thanks to the efforts of many, the field of reproductive medicine has grown, advanced, and progressed in ways that seemed nearly impossible just a few decades ago., (Copyright © 2018. Published by Elsevier Inc.)

The aim of this retrospective cohort study was to assess differences in infertility-related baseline characteristics and IVF outcome between European and Middle Eastern/North African (MENA) patients. Of 2703 patients undergoing their first IVF cycle, 2485 were Caucasian of European descent and 218 originated from the MENA region. MENA patients were significantly younger (30.6 versus 34.0 years, P < 0.001), less likely smokers, with higher body mass indexes. Infertility duration was longer in MENA patients (P < 0.001), their male partners were younger (P < 0.001) and smoked more often than European male patients (P = 0.005). Male factor infertility (P = 0.017) and polycystic ovary syndrome (PCOS; P = 0.032) was more prevalent in MENA patients, showed significantly higher basal FSH concentrations (P = 0.012) and significantly fewer oocytes retrieved (RR 0.83, 95% CI 0.74-0.93, P = 0.001). Clinical pregnancy rates were comparable (22.4% [European] versus 22.9% [MENA]). Fewer MENA patients had surplus embryos cryopreserved (OR 0.41, 95% CI 0.22-0.76, P = 0.004). Despite younger age and higher prevalence of PCOS, MENA patients had significantly lower oocyte yields than their European counterparts (P = 0.001). These findings suggest a more rapid decline in ovarian function in women of MENA descent., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005.

Background: Oocyte retrieval for in vitro fertilization (IVF) is one of the most common minor surgical procedures., Objectives: To give an update on anesthesia practices used currently in the United States and Europe in assisted reproductive technology, and discuss the safety or the potential risks for oocyte and embryo quality., Search Strategy: Electronic search of MEDLINE for literature published between 1972 and 2008., Selection Criteria: Relevant studies on the types of anesthesia used for oocyte retrieval and the impact on oocyte and embryo quality., Data Collection and Analysis: Relevant studies were reviewed by the authors and the ones of significant scientific merit, based on methodology, were included., Main Results: Types of anesthesia that may be used for transvaginal follicular aspiration and oocyte retrieval include: general anesthesia, neuraxial anesthesia, conscious sedation, injection of local anesthetic agents into the cervix or the vaginal wall, or any combination of the above. Conscious sedation is most commonly used in IVF because it is relatively safe and does not require the presence of an anesthesiologist when opioids or benzodiazepines are used. Propofol is the preferred anesthetic agent, but should be used by specially trained personnel., Conclusion: Conscious sedation is the most popular method of anesthesia used in IVF. Presently, a combination of propofol, fentanyl, and midazolam is used frequently. It is easy to administer in cooperative and motivated patients and is safe in healthy individuals; it has a relatively low risk for adverse effects on oocyte and embryo quality and pregnancy rates.

Human embryonic stem cell (hESC)-based cell therapy depends on access to surplus embryos from IVF cycles and collaborative interactions between biomedical researchers and reproductive medicine professionals. It is becoming instrumental to achieve an international consensus about the standards that should regulate the manipulation of human embryonic tissue in two distinct settings: reproductive medicine and embryonic stem cell research. Within hESC research, the regulatory framework needs to be adjusted according to the actual expectations and potential detrimental consequences of hESC research.

In Antwerp, single embryo transfers (SET) have increased, and this change in policy has seen the incidence of singletons rise from 70 to 90%, twins drop from 25 to 10%, and triplets drop from 1-2% to none at all. At a national and regional level, changes have been much more dramatic as a result of a change in the law in 2003 mandating SET. Data show a huge increase in the number of treatment cycles and a dramatic rise in SET. Rates of twins and triplets have dropped considerably. European data indicate wide differences in the incidence of triplets between countries, varying between 0% (e.g.Slovenia, Iceland, Lithuania) and 4.4% (Hungary), but almost nothing is known about the true incidence of fetal reduction. US data indicate some decrease in triplets during recent years, but certainly nowhere near elimination. These data suggest that in some countries, IVF triplets have almost been eliminated, but the problem is masked by significant fetal reductions. Where SET is not widely used, triplets are still frequent. A correlation appears to exist between the percentage of SET cycles and the incidence of triplets. It is suggested that the solution to almost totally eliminate triplets after IVF is single embryo transfer.

European results of assisted reproductive techniques (ART) from treatments initiated during 2002 are presented in this sixth report. Data was mainly collected from already existing national registers. From 25 countries, 631 clinics reported 324,238 treatment cycles with: IVF 122,634, ICSI 135,048, frozen embryo replacement (FER) 57 162, egg donation (ED) 7677, preimplantation genetic diagnosis/screening (PGD/PGS) 1563 and in vitro maturation (IVM) 154. Overall this represents a 12% increase since year 2001. For the second time, results on European data on intrauterine inseminations were reported from 17 countries. A total of 93,284 cycles [IUI-husband/partner (H), 78 505 and IUI-donor (D), 14,779] were included. In 13 countries where all clinics reported to the register, a total of 177,429 cycles were performed in a population of 193.7 million, corresponding to 916 cycles per million inhabitants. For IVF the clinical pregnancy rate per aspiration and per transfer was 26.0 and 29.5%, respectively. For ICSI the corresponding rates were 27.2 and 29.4%. These figures are marginally better than in 2001. After IUI-H the clinical pregnancy rate was 11.6% in women below 40 and 7.8% in women>or=40 years of age. After IVF and ICSI the distribution of transfer of 1, 2, 3 and 4 or more embryos was 13.7, 54.8, 26.9 and 4.7%, respectively. Compared with year 2001, less embryos were transferred, but huge differences existed between countries. The distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 75.5, 23.2 and 1.3%, respectively. This gives a total multiple delivery rate of 24.5%, compared with 25.5% in year 2001. The range of triplet deliveries after IVF and ICSI varied from 0.0 to 5.2% between countries. After IUI-H in women below 40 years of age, 10.2% were twin and 1.3% triplet gestations.

European results of assisted reproductive techniques from treatments initiated during 2001 are presented in this fifth report. Data were collected mainly from already existing national registers. From 23 countries, 579 clinics reported 289 690 cycles with: IVF 120 946, ICSI 114 378, frozen embryo transfer (FER) 47 195 and egg donation (ED) 7171. Overall this represents a 4% increase since the year 2000. For the first time, results on European data on intra-uterine inseminations (IUIs) were reported from 15 countries. A total of 67 124 cycles [IUI husband'sperm (IUI-H) 52 949 and IUI donor sperm (IUI-D) 14 185] were included. In 12 countries where all clinics reported to the register, a total of 108 910 cycles were performed in a population of 131.4 million, corresponding to 829 cycles per million inhabitants. For IVF, the clinical pregnancy rate per aspiration and per transfer was 25.1 and 29.0%, respectively. For ICSI, the corresponding rates were 26.2 and 28.3%. These figures are similar to the results from 2000. After IUI-H, the clinical pregnancy rate was 12.8% in women <40 and 9.7% in women > or =40 years of age. After IVF and ICSI, the distribution of transfer of one, two, three and > or =4 embryos was 12.0, 51.7, 30.8 and 5.5%, respectively. Compared with the year 2000, fewer embryos were transferred, but huge differences existed between countries. The distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 74.5, 24.0 and 1.5%, respectively. This gives a total multiple delivery rate of 25.5%, compared with 26.9% in the year 2000. The range of triplet deliveries after IVF and ICSI differed from 0.0 to 8.2% between countries. After IUI-H in women <40 years of age, 10.2% were twin and 1.1% were triplet gestations.

This review considers the value of single embryo transfer (SET) to prevent multiple pregnancies (MP) after IVF/ICSI. The incidence of MP (twins and higher order pregnancies) after IVF/ICSI is much higher (approximately 30%) than after natural conception (approximately 1%). Approximately half of all the neonates are multiples. The obstetric, neonatal and long-term consequences for the health of these children are enormous and costs incurred extremely high. Judicious SET is the only method to decrease this epidemic of iatrogenic multiple gestations. Clinical trials have shown that programmes with >50% of SET maintain high overall ongoing pregnancy rates ( approximately 30% per started cycle) while reducing the MP rate to <10%. Experience with SET remains largely European although the need to reduce MP is accepted worldwide. An important issue is how to select patients suitable for SET and embryos with a high putative implantation potential. The typical patient suitable for SET is young (aged <36 years) and in her first or second IVF/ICSI trial. Embryo selection is performed using one or a combination of embryo characteristics. Available evidence suggests that, for the overall population, day 3 and day 5 selection yield similar results but better than zygote selection results. Prospective studies correlating embryo characteristics with documented implantation potential, utilizing databases of individual embryos, are needed. The application of SET should be supported by other measures: reimbursement of IVF/ICSI (earned back by reducing costs), optimized cryopreservation to augment cumulative pregnancy rates per oocyte harvest and a standardized format for reporting results. To make SET the standard of care in the appropriate target group, there is a need for more clinical studies, for intensive counselling of patients, and for an increased sense of responsibility in patients, health care providers and health insurers.

Oocyte donation (OD), a technique successfully used in Assisted reproductive techniques (ART), has been effective for 20 years as the palliative treatment of certain exocrine ovarian failures. Its indications have also been extended to cover some genetic diseases and documented occult ovarian insufficiency. In France, after an extensive judicial and ethical deliberation, OD was deemed legal and its practice was proscribed in the Bioethics Laws 94-653 and 94-654 of 29 July 1994. Its essential underlying principles are: voluntary, free, anonymous and confidential OD; according to a French decree to meet safety concerns, OD-derived embryos must be quarantined for six months. In vitro fertilization (IVF) programs using donated oocytes are conducted in authorized centers under the responsibility of physicians authorized to retrieve and manipulate donated oocytes. The managers of these programs are the system's keystone, as their role includes, among other, the verification of indications, legal documents, public health safety, anonymous pairing of donor and recipient, and the collection of outcome data. At present, depending of the year, French programs have achieved 17-22% clinical pregnancy rates from transferred OD-derived frozen-thawed embryos, and follow-up studies reported excellent results concerning family relationships, and the physical and psychological development of the children. However, difficulties encountered in the daily practice of OD have led concerned physicians to form the Study group for OD (GEDO) to explore different topics with the aim of improving the overall management of this form of ART. We discussed these points herein, in comparison with the approaches of other European countries.

The dramatic increase in the incidence of high order multiple pregnancies that has occurred since the mid-1970s is due to three main factors: increasing female age at conception; increasing use of ovulation induction agents and the introduction of sophisticated assisted reproduction techniques. High order multiple pregnancies are at significantly higher risk of complications than singleton pregnancies, for the fetuses, babies and the mothers. The aim of all fertility treatments is to achieve a healthy live child for each couple seeking treatment. Treatment of infertility by IVF and related techniques provides an ideal opportunity to limit the number of high order multiple pregnancies by reducing the number of embryos transferred to the woman. The realization that high order multiple pregnancy can and should be avoided has increasingly led, in most European countries, to a restriction of the number of embryos for transfer to two or even one, without a significant decrease in a couples' chance of achieving a pregnancy. The experience of European countries in reducing the number of embryos transferred is reviewed and a recommendation made that a responsible attitude to embryo transfer is adopted by all practitioners of assisted reproduction.