Pregnancy following assisted reproductive technology in morbidly obese patients: assessment of feto-maternal outcomes.

PURPOSE: To examine feto-maternal characteristics and outcomes of morbidly obese pregnant patients who conceived with assisted reproductive technology (ART). METHODS: This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. Study population was 48,365 patients with ART pregnancy from January 2012 to September 2015, including non-obesity (n = 45,125, 93.3%), class I-II obesity (n = 2445, 5.1%), and class III obesity (n = 795, 1.6%). Severe maternal morbidity at delivery per the Centers for Disease and Control Prevention definition was assessed with multivariable binary logistic regression model. RESULTS: Patients in the class III obesity group were more likely to have a hypertensive disorder (adjusted-odds ratio (aOR) 3.03, 95% confidence interval (CI) 2.61-3.52), diabetes mellitus (aOR 3.08, 95%CI 2.64-3.60), large for gestational age neonate (aOR 3.57, 95%CI 2.77-4.60), and intrauterine fetal demise (aOR 2.03, 95%CI 1.05-3.94) compared to those in the non-obesity group. Increased risks of hypertensive disease (aOR 1.35, 95%CI 1.14-1.60) and diabetes mellitus (aOR 1.39, 95%CI 1.17-1.66) in the class III obesity group remained robust even compared to the class I-II obesity group. After controlling for priori selected clinical, pregnancy, and delivery factors, patients with class III obesity were 70% more likely to have severe maternal morbidity at delivery compared to non-obese patients (8.2% vs 4.4%, aOR 1.70, 95%CI 1.30-2.22) whereas those with class I-II obesity were not (4.1% vs 4.4%, aOR 0.87, 95%CI 0.70-1.08). CONCLUSIONS: The results of this national-level analysis in the United States suggested that morbidly obese pregnant patients conceived with ART have increased risks of adverse fetal and maternal outcomes.

Long-term healthcare utilization and costs of babies born after assisted reproductive technologies (ART): a record linkage study with 10-years' follow-up in England.

STUDY QUESTION: Is the long-term health care utilization of children born after ART more costly to the healthcare system in England than children born to mothers with no fertility problems? SUMMARY ANSWER: Children born after ART had significantly more general practitioner (GP) consultations and higher primary care costs up to 10 years after birth, and significantly higher hospital admission costs in the first year after birth, compared to children born to mothers with no fertility problems. WHAT IS KNOWN ALREADY: There is evidence that children born after ART are at an increased risk of adverse birth outcomes and a small increased risk of rare adverse outcomes in childhood. STUDY DESIGN, SIZE, DURATION: We conducted a longitudinal study of 368 088 mother and baby pairs in England using a bespoke linked dataset. Singleton babies born 1997-2018, and their mothers, who were registered at GP practices in England contributing data to the Clinical Practice Research Datalink (CPRD), were identified through the CPRD GOLD mother-baby dataset; this data was augmented with further linkage to the mothers' Human Fertilisation and Embryology Authority (HFEA) Register data. Four groups of babies were identified through the mothers' records: a 'fertile' comparison group, an 'untreated sub-fertile' group, an 'ovulation induction' group, and an ART group. Babies were followed-up from birth to 28 February 2021, unless censored due to loss to follow-up (e.g. leaving GP practice, emigration) or death. PARTICIPANTS/MATERIALS, SETTING, METHODS: The CPRD collects anonymized coded patient electronic health records from a network of GPs in the UK. We estimated primary care costs and hospital admission costs for babies in the four fertility groups using the CPRD GOLD data and the linked Hospital Episode Statistics (HES) Admitted Patient Care (APC) data. Linear regression was used to compare the care costs in the different groups. Inverse probability weights were generated and applied to adjust for potential bias caused by attrition due to loss to follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: Children born to mothers with no fertility problems had significantly fewer consultations and lower primary care costs compared to the other groups throughout the 10-years' follow up. Regarding hospital costs, children born after ART had significantly higher hospital admission costs in the first year after birth compared to those born to mothers with no fertility problems (difference = £307 (95% CI: 153, 477)). The same pattern was observed in children born after untreated subfertility and ovulation induction. LIMITATIONS, REASONS FOR CAUTION: HFEA linkage uses non-donor data cycles only, and the introduction of consent for data use reduced the availability of HFEA records after 2009. The fertility groups were derived by augmenting HFEA data with evidence from primary care records; however, there remains some potential misclassification of exposure groups. The cost of neonatal critical care is not captured in the HES APC data, which may cause underestimation of the cost differences between the comparison group and the infertility groups. WIDER IMPLICATIONS OF THE FINDINGS: The findings can help anticipate the financial impact on the healthcare system associated with subfertility and ART, particularly as the demand for these treatments grows. STUDY FUNDING/COMPETING INTEREST(S): C.C. and this work were funded by a UK Medical Research Council Career Development Award [MR/L019671/1] and a UK MRC Transition Support Award [MR/W029286/1]. X.H. is an Australia National Health and Medical Research Council (NHMRC) Emerging Leadership Fellow [grant number 2009253]. The authors declare no competing interest. TRIAL REGISTRATION NUMBER: N/A.

Risk assessment of assisted reproductive technology and parental age at childbirth for the development of uniparental disomy-mediated imprinting disorders caused by aneuploid gametes.

BACKGROUND: Our previous study suggested that assisted reproductive technology (ART) may be a possible risk factor for the development of epimutation-mediated imprinting disorders (epi-IDs) for mothers aged ≥ 30 years. However, whether ART or advanced parental age facilitates the development of uniparental disomy-mediated IDs (UPD-IDs) has not yet been investigated. RESULTS: We enrolled 130 patients with aneuploid UPD-IDs including various IDs confirmed by molecular studies and obtained ART data of the general population and patients with epi-IDs from a robust nationwide database and our previous report, respectively. We compared the proportion of ART-conceived livebirths and maternal childbearing age between patients with UPD-IDs and the general population or patients with epi-IDs. The proportion of ART-conceived livebirths in patients with aneuploid UPD-IDs was consistent with that in the general population of maternal age ≥ 30 years and was lower than that in the patients with epi-IDs, although there was no significant difference. The maternal childbearing age of patients with aneuploid UPD-IDs was skewed to the increased ages with several cases exceeding the 97.5th percentile of maternal childbearing age of the general population and significantly higher than that of patients with epi-IDs (P < 0.001). In addition, we compared the proportion of ART-conceived livebirths and parental age at childbirth between patients with UPD-IDs caused by aneuploid oocytes (oUPD-IDs) and that by aneuploid sperm (sUPD-IDs). Almost all ART-conceived livebirths were identified in patients with oUPD-IDs, and both maternal age and paternal age at childbirth were significantly higher in patients with oUPD-IDs than in patients with sUPD-IDs. Because maternal age and paternal age were strongly correlated (rs = 0.637, P < 0.001), higher paternal age in oUPD-IDs was explained by the higher maternal age in this group. CONCLUSIONS: Different from the case of epi-IDs, ART itself is not likely to facilitate the development of aneuploid UPD-IDs. We demonstrated that advanced maternal age can be a risk factor for the development of aneuploid UPD-IDs, particularly oUPD-IDs.

Assessment of abnormal placentation in pregnancies conceived with assisted reproductive technology.

OBJECTIVE: To examine the association between assisted reproductive technology (ART) and abnormal placentation. METHODS: This is a retrospective cohort study querying the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample. The study population included 14, 970, 064 deliveries for national estimates from January 2012 to September 2015. The exposure was 48, 240 pregnancies after ART. The main outcome measure encompassed three abnormal placentation pathologies (placenta previa [PP], placenta accreta spectrum [PAS], and vasa previa [VP]). Propensity score matching was performed to assess the exposure-outcome association. RESULTS: Pregnancy after ART was more likely to have a diagnosis of PAS (2.8 vs 1.0 per 1000 deliveries; adjusted odds ratio [aOR], 2.06 [95% confidence interval (CI), 1.44-2.93]), PP (24.5 vs 8.6 per 1000; aOR, 2.98 [95% CI, 2.64-3.35]), and VP (2.3 vs <0.3 per 1000; aOR, 11.3 [95% CI, 5.86-21.8]) compared with pregnancy without ART. Similarly, pregnancy after ART was associated with an increased likelihood of having multiple types of abnormal placentation, including VP with PP (aOR, 15.4 [95% CI, 6.15-38.4]) and PAS with PP (aOR, 2.80 [95% CI, 1.32-5.92]) compared with non-ART pregnancy. CONCLUSIONS: This national-level analysis suggests that pregnancy after ART is associated with a significantly increased risk of abnormal placentation, including PAS, PP, and VP.

Ethnic group and reason for assisted reproductive technology failure: analysis of the Human Fertilisation and Embryology Authority registry data from 2017 to 2018.

OBJECTIVE: To understand how the risk of different assisted reproductive technology (ART) failure types varies by ethnic group and explore the role of mediation by maternal age and suspected etiology. DESIGN: An observational study of 48,750 women who undertook treatment with ART in the United Kingdom between January 2017 and December 2018. SETTING: The Human Fertilisation and Embryology Authority national ART registry of the United Kingdom. PATIENT(S): Women who commenced a first cycle of ART for the purpose of primary fresh embryo transfer using their own oocytes were included. INTERVENTION(S): Maternal ethnic group. MAIN OUTCOME MEASURE(S): The ART failure types were modeled on the maternal ethnic group using the Poisson regression to produce relative risks (RRs) with 95% confidence intervals. The potential indirect effects of maternal age and etiology of subfertility were estimated, and the RRs with 95% confidence intervals were produced. RESULT(S): Black women were at greater risk of treatment failure with respect to live birth than women who were white: cycle cancellation, RR of 2.15 (1.78-2.62); failed fertilization, RR of 2.36 (1.90-2.93); unintended freeze-all, RR of 1.71 (1.43-2.05); failed implantation, RR of 1.23 (1.12-1.34); and pregnancy loss, RR of 1.38 (1.15-1.64). Women who were Asian were at moderately increased risk: RRs of 1.31 (1.17-1.47), 1.60 (1.42-1.80), 1.25 (1.14-1.38), 1.11 (1.07-1.16), and 1.13 (1.03-1.23), across the same outcomes, respectively. Inequality may have been reduced had women of all ethnicities initiated treatment at the same age. CONCLUSION(S): Black women were at greatest risk of all failure types, and women who were Asian were at intermediate risk compared with women who were white. Some of the risks among women who were black may be mediated by maternal age.

Female fertility treatment and adverse birth outcomes: a multistate analysis of pregnancy risk assessment monitoring system data.

OBJECTIVE: The popularity of fertility treatments has continued to rise, however, the potential health risks of these treatments for both mother and infant are not fully known. Our objective was to determine the association between fertility treatments and adverse birth outcomes of intended pregnancies using the Pregnancy Risk Assessment Monitoring System (PRAMS) data. METHODS: Data from 27,018 intended pregnancies, collected from 2009 to 2018 in the United States, were included in our analysis. PRAMS data consisted of questionnaire and birth certificate data. SAS 9.4 was used for analyses accounting for complex survey weights. All analyses were conducted separately for singleton and twin births. Weighted percentages with 95% confidence intervals (CIs) were estimated for maternal characteristics and birth outcomes. Multivariable logistic regression was used to determine adjusted odds ratios (OR) and 95% CIs for associations of fertility treatment use and adverse birth outcomes. RESULTS: Close to 12% of women reported the use of any fertility treatment. Among those using fertility treatments, the most common type was assisted reproductive technology (ART) for both twin (68.7%, 95% CI: 62.3, 75.2) and singleton births (45.1%, 95% CI: 42.0, 48.1). Use of any type of fertility treatment for singleton births was associated with increased odds of a cesarean delivery (OR: 1.31, 95% CI: 1.16, 1.47), preterm birth (OR: 1.42, 95% CI: 1.20, 1.67), a small-for-gestational age infant (OR: 1.20, 95% CI: 1.00, 1.44), and an infant hospital stay >5 days (OR: 1.34, 95% CI: 1.11, 1.62). Use of fertility treatment for twin births was associated with cesarean delivery only. In analyses examining associations for specific types of treatment (medication alone, ART, insemination) with birth outcomes, results varied by treatment type. CONCLUSIONS: In this large population-based sample of women who intended to become pregnant and had a live birth, fertility treatment was associated with adverse birth outcomes. Patients seeking fertility treatment should be appropriately counseled on the risks of adverse maternal and infant birth outcomes overall and by treatment type. Maternal support and resources to prevent adverse birth outcomes among women using fertility treatments are warranted.

Learning from incidents in medically assisted reproduction: the Notify Library as a learning tool.

Biovigilance is the systematic monitoring of serious adverse reactions and events (SARE) that ensures the quality and safety of tissues and cells for human application in medically assisted reproduction (MAR). The Notify Library is an open access database launched by the World Health Organization and supported by the Italian National Transplant Centre (CNT) that has collected information on documented adverse occurrences in transplantation, transfusion and MAR. It is not a SARE register, but rather a collection of SARE types identified primarily by review of published articles and case reports from national or regional vigilance programmes. The Notify Library includes many well-documented records of adverse occurrences in MAR treatment, representing a useful tool for MAR operators in the evaluation of the risks associated with the clinical application of reproductive tissues and cells. It is updated with new records when a new type of incident is reported for the first time. All incident types described might have teaching value during the risk management carried out by a MAR centre. Sharing lessons learned from these incidents represents an important didactic opportunity that can help MAR centres to improve their processes and to achieve higher standards of quality and safety.

Selecting the optimal gestational carrier: medical, reproductive, and ethical considerations.

The goals of a gestational surrogacy relationship are to have a healthy baby for the intended parents while maintaining the medical and psychological well-being of the gestational carrier. A successful gestational surrogacy relationship will result also in good psychosocial outcomes for the gestational carrier, intended parents, and child. Finding a gestational carrier who will achieve these goals would be the ideal. This article focuses on key medical, reproductive, and ethical considerations to optimize clinical outcomes in gestational carrier cycles. Recommendations from available clinical guidelines regarding gestational surrogacy are reviewed, along with updates from current literature.

Gestational surrogacy: medical, psychosocial, and legal considerations.

Gestational surrogacy can provide an effective family-building method for women whose uterus is absent or dysfunctional and with contraindications to pregnancy, single men, and same-sex male couples. Over the past 30 years, gestational surrogacy cases have represented a growing percentage of third-party reproduction cases, both in the United States and internationally. The following series of articles provides a summary of current topics in optimizing GS arrangements. They focus on medical and psychological screening; psychosocial adjustment of carriers, children, and their families; legal considerations with precedent-setting cases that every clinician should know; and an international overview of cross-border surrogacy.

Pregnancy loss: A 40-year nationwide assessment.

INTRODUCTION: Pregnancy loss is frequent. We aimed to assess the frequency and trends in pregnancy losses according to female age and mode of conception over a 40-year follow-up period. MATERIAL AND METHODS: In a national historical prospective cohort study, we followed all Danish women 10-49 years over the 40-year study period 1978-2017. Data on pregnancies and their outcomes were obtained from the National Health Registry, the Medical Birth Registry and the National Fertility Registry. Incidence rates per 100 pregnancies and per 1,000 women-years as well as lifetime risks per 100 women were calculated. Women included in the lifetime analysis were followed from age 12 to age 49. Pregnancy loss included spontaneous abortion, missed abortion and anembryonic pregnancy. RESULTS: In 3 519 455 recorded pregnancies, 337 008, or 9.6%, were diagnosed with a pregnancy loss. The proportion increased from 7.5% in 1978-1979, peaked at 10.7% in 2000 and thereafter decreased to 9.1% in 2015-2017. Pregnancy loss rate in women 10-14 years was 3.9%, increasing gradually with age to 26.9% in pregnant women 45-49 years, a 6.9-fold increase. Loss rates were slightly lower in naturally conceived pregnancies than in assisted pregnancies except for women above 45 years, where the risk of loss was higher in the spontaneously conceived group. Lifetime risk of specific numbers of losses were: 0: 76.9%, 1: 17.9%, 2: 3.9%, 3: 0.87%, and 4+: 0.35%. CONCLUSIONS: The proportion of women experiencing pregnancy loss has changed little throughout four decades and is still primarily influenced by female age. More than 75% of pregnant women are never recorded with a pregnancy loss, and <1.5% will experience three or more losses.

[Assessment of psychomotor development of Spanish children up to 3 years of age conceived by assisted reproductive techniques: Prospective matched cohort study]. / Evaluación del desarrollo psicomotor hasta los 3 años de edad de niños españoles concebidos por técnicas de reproducción asistida (FIV/ICSI): estudio prospectivo de cohorte controlado.

INTRODUCTION: More than five million children have been conceived by assisted reproductive techniques (ART) around the world. Most authors agree that there are no differences in psychomotor development in comparison to naturally conceived children. However, these results are still contradictory. OBJECTIVE: To determine whether children born from a cohort of ART-clinical gestations have a higher risk of suffering neurodevelopmental disorders in comparison to a control group. The potential associated ART-factors associated were also determined. MATERIAL AND METHODS: The study included the assessment of children up to 3 years old conceived by ART, and born from a cohort of women treated by the reproduction unit of a public hospital from May 2012 to May 2014. A simultaneous assessment was made of matched controls, by following the newborn naturally conceived after the ART-case, of the same group of maternal age, gestational age, and type of gestation. RESULTS: There were 243 clinical gestations and 267 ART-newborns, of which 231 were assessed (87%). A simultaneous assessment was carried out in 208/230 controls (90%). There were no differences in neurodevelopmental disorders (global developmental delay, autism spectrum or language delay). Multivariate analysis of potential ART factors only showed an association between transfer of frozen embryos with language delay that has not been previously described. CONCLUSIONS: There were no differences between groups after adjusting the results according to maternal age, multiple pregnancy, and other possible confounding factors, supporting that the role of these factors may be more relevant than the ART itself. The association between frozen embryo transfer and language delay has not been previously described. Thus, more studies are needed to confirm or refute this relationship.

Genome-wide assessment of DNA methylation in mouse oocytes reveals effects associated with in vitro growth, superovulation, and sexual maturity.

BACKGROUND: In vitro follicle culture (IFC), as applied in the mouse system, allows the growth and maturation of a large number of immature preantral follicles to become mature and competent oocytes. In the human oncofertility clinic, there is increasing interest in developing this technique as an alternative to ovarian cortical tissue transplantation and to preserve the fertility of prepubertal cancer patients. However, the effect of IFC and hormonal stimulation on DNA methylation in the oocyte is not fully known, and there is legitimate concern over epigenetic abnormalities that could be induced by procedures applied during assisted reproductive technology (ART). RESULTS: In this study, we present the first genome-wide analysis of DNA methylation in MII oocytes obtained after natural ovulation, after IFC and after superovulation. We also performed a comparison between prepubertal and adult hormonally stimulated oocytes. Globally, the distinctive methylation landscape of oocytes, comprising alternating hyper- and hypomethylated domains, is preserved irrespective of the procedure. The conservation of methylation extends to the germline differential methylated regions (DMRs) of imprinted genes, necessary for their monoallelic expression in the embryo. However, we do detect specific, consistent, and coherent differences in DNA methylation in IFC oocytes, and between oocytes obtained after superovulation from prepubertal compared with sexually mature females. Several methylation differences span entire transcription units. Among these, we found alterations in Tcf4, Sox5, Zfp521, and other genes related to nervous system development. CONCLUSIONS: Our observations show that IFC is associated with altered methylation at specific set of loci. DNA methylation of superovulated prepubertal oocytes differs from that of superovulated adult oocytes, whereas oocytes from superovulated adult females differ very little from naturally ovulated oocytes. Importantly, we show that regions other than imprinted gDMRs are susceptible to methylation changes associated with superovulation, IFC, and/or sexual immaturity in mouse oocytes. Our results provide an important reference for the use of in vitro growth and maturation of oocytes, particularly from prepubertal females, in assisted reproductive treatments or fertility preservation.

Introduction: Add-ons for assisted reproductive technology: can we be honest here?

Adjuncts, more often known as add-ons, are now part of the landscape of an in vitro fertilization cycle. Since the early days of in vitro fertilization, fertility services have rightly been seeking improved success rates. At present there are a multitude of choices for patients who are usually presented with a menu of add-ons to choose from. This is driven by the desire to give patients the best chances of becoming parents. This Views and Reviews series discusses all aspects of add-ons. It is not exhaustive as even as we are finishing the preparation of the series, there is a new study about the use of cytokines as an add-on. The overall conclusion from this series of articles is that despite considerable efforts to establish benefits with add-ons that there is a paucity of data when we consider the outcome of live birth.

Do à la carte menus serve infertility patients? The ethics and regulation of in vitro fertility add-ons.

Add-on treatments are the new black. They are provided (most frequently, sold) to patients undergoing in vitro fertilization on the premise that they will improve the chances of having a baby. However, the regulation of add-ons is consistently minimal, meaning that they are introduced into routine practice before they have been shown to improve the live birth rate. Debate on the adequacy of this light-touch approach rages. Defenders argue that demands for a rigorous approval process are paternalistic, as this would delay access to promising treatments. Critics respond that promising treatments may turn out to have adverse effects on patients and their offspring, contradicting the clinician's responsibility to do no harm. Some add-ons, including earlier versions of preimplantation genetic testing for aneuploidy, might even reduce the live birth rate, raising the prospect of desperate patients paying more to worsen their chances. Informed consent represents a solution in principle, but in practice there is a clear tension between impartial information and direct-to-consumer advertising. Because the effects of a treatment cannot be known until it has been robustly evaluated, we argue that strong evidence should be required before add-ons are introduced to the clinic. In the meantime, there is an imperative to identify methods for communicating the associated risks and uncertainties of add-ons to prospective patients.

Cost-effectiveness of preimplantation genetic testing for aneuploidies.

OBJECTIVE: To evaluate the economical benefit of preimplantation genetic testing of aneuploidies (PGT-A) when applied in an extended culture and stringent elective single ET framework. DESIGN: Theoretical cost-effectiveness study. SETTING: Not applicable. PATIENTS/ANIMAL(S): None. INTERVENTION(S): Comparison of the cost-effectiveness between two IVF treatment strategies: serial transfer of all available blastocysts without genetic testing (first fresh transfer and subsequent frozen-thawed transfer); and systematic use of genetic testing (trophectoderm biopsy, freeze-all, and frozen-thawed transfers of euploid blastocysts). The costs considered for this analysis are based on regional public health system provider. MAIN OUTCOME MEASURE(S): Costs per live birth. RESULT(S): Cost-effectiveness profile of PGT-A improves with female age and number of available blastocysts. Sensitivity analyses varying the costs of ET, the costs of genetic analyses, the magnitude of the detrimental impact of PGT-A on live birth rate, and the crude live birth rates change to some extent the thresholds for effectiveness but generally confirm the notion that PGT-A can be economically advantageous in some specific subgroups. CONCLUSION(S): PGT-A can be cost-effective in specific clinical settings and population groups. Economic considerations deserve attention in the debate regarding the clinical utility of PGT-A.

[Medically Assisted Reproduction in Natural Cycle: Outcome Evaluation of a Reproductive Medicine Department]. / Procriação Medicamente Assistida em Ciclo Natural: Avaliação dos Resultados de um Departamento de Medicina da Reprodução.

INTRODUCTION: Medically assisted reproduction in natural cycle has been investigated, especially in women with poor response to conventional ovarian stimulation, with endometrial receptivity improvement, lower cost and possibility of successive cycles. The disadvantages are: lower profitability per treatment cycle and higher cancellation rate. The aim of this study was to determine the rate of clinical pregnancy in infertile women subjected to medically assisted reproduction in natural cycle. MATERIAL AND METHODS: Retrospective study of 149 medically assisted reproduction without ovarian stimulation of 50 infertile women, between January/2011 and October/2014. RESULTS: The mean age of women undergoing medically assisted reproduction in natural cycle was 36.1 years. Approximately half (46.0%) of the cycles were performed in poor responders. On the day of ovulation trigger, the mean diameter of the follicle was 17.5 mm. Twenty-three cycles (15.4%) were canceled prior to ovulation trigger. In 8 cycles (5.3%), ovulation occurred between ovulation trigger and oocyte retrieval. In the majority of cycles (n = 118; 79.2%) oocyte retrieval was executed, a medically assisted reproduction technique was performed in 71 (47.6%), mostly intracytoplasmic injection. The overall fertilization rate was 77.5%. In 40 cycles (26.8%) there was embryo transfer. The implantation rate and the clinical pregnancy rate by embryo transfer was 35.0% and 25.0%, respectively. Most pregnancies occurred in poor responders, according to Bologna criteria. DISCUSSION: Although the pregnancy rate per cycle started was 6.7%, the rate of clinical pregnancy per embryo transfer is quite satisfactory, being a group of women with unfavorable responses in previous treatments. The relatively high rates of cycle cancellation are mitigated by the greater simplicity and lower cost of these cycles. CONCLUSION: The results obtained in this study demonstrate that Medically Assisted Reproduction in natural cycle may be an alternative treatment for ovarian stimulation in patients with poor prognosis, whose only alternative would be oocyte donation.

Introdução: As técnicas de procriação medicamente assistida em ciclo natural têm sido investigadas, sobretudo em mulheres com má resposta à estimulação ovárica convencional, observando-se melhor recetividade endometrial, custo inferior e possibilidade de realização de ciclos sucessivos. Como desvantagens salientam-se: menor eficácia por ciclo de tratamento e maior taxa de cancelamento. O objetivo definido para este trabalho foi determinar a taxa de gravidez evolutiva em mulheres inférteis, submetidas a procriação medicamente assistida em ciclo natural. Material e Métodos: Estudo retrospetivo de 149 ciclos de procriação medicamente assistida sem estimulação ovárica de 50 mulheres inférteis, entre janeiro de 2011 e outubro de 2014. Resultados: As mulheres submetidas a procriação medicamente assistida em ciclo natural tinham, em média, 36,1 anos. Aproximadamente metade (46,0%) dos ciclos realizaram-se em más respondedoras. No dia do desencadeamento da ovulação o diâmetro médio do folículo foi 17,5 mm. Cancelaram-se 23 ciclos (15,4%) previamente ao desencadeamento. Em 8 ciclos (5,3%) ocorreu ovulação entre o desencadeamento e a punção folicular. Na maioria dos ciclos (n = 118; 79,2%) efetuou-se punção folicular, realizando-se técnica de procriação medicamente assistida em 71 (47,6%), maioritariamente injeção intracitoplasmática. A taxa de fecundação global foi 63,8%. Em 40 ciclos (26,8%) houve transferência embrionária. A taxa de implantação e de gravidez evolutiva por transferência embrionária foram de 35,0% e 25,0%, respetivamente. A maioria das gestações ocorreu em más respondedoras, conforme critérios de Bolonha. Discussão: Apesar de a taxa de gravidez por ciclo iniciado ser de 6,7%, a taxa de gravidez evolutiva por transferência embrionária é bastante satisfatória, sendo mulheres com respostas desfavoráveis em tratamentos prévios. As taxas relativamente elevadas de cancelamento do ciclo são atenuadas pela simplicidade e menor custo destes ciclos. Conclusão: Os resultados obtidos neste trabalho demonstram que as técnicas de procriação medicamente assistida em ciclo natural podem ser uma alternativa de tratamento à estimulação ovárica em doentes com mau prognóstico, cuja alternativa seria o recurso à doação de ovócitos.

A 50% reduction in multiple live birth rate is associated with a 13% cost saving: a real-life retrospective cost analysis.

Belgian legislation limiting the number of embryos for transfer has been shown to result in a 50% reduction of the multiple live birth rate (MLBR) per cycle without having a negative impact on the cumulative delivery rate per patient within six cycles or 36 months. The objective of the current study was to evaluate the cost saving associated with a 50% reduction in MLBR. A retrospective cost analysis was performed of 213 couples, who became pregnant and had a live birth after one or more assisted reproductive technology treatment cycles, and their 254 children. The mean cost of a singleton (n = 172) and multiple (n = 41) birth was calculated based on individual hospital invoices. The cost analysis showed a significantly higher total cost (assisted reproductive technology treatment, pregnancy follow-up, delivery, child cost until the age of 2 years) for multiple births (both children: mean €43,397) than for singleton births (mean: €17,866) (Wilcoxon-Mann-Whitney P < 0.0001). A 50% reduction in MLBR resulted in a significant cost reduction related to hospital care of 13%.

Outcomes of medical malpractice claims in assisted reproductive technology over a 10-year period from a single carrier.

OBJECTIVE: Medical malpractice claims vary by specialty. Contributory factors to malpractice in reproductive endocrinology and infertility (REI) are not well defined. We sought to determine claims' frequency, basis of claims, and outcomes of settled claims in REI. DESIGN: This is a retrospective, descriptive review of 10 years of claims. SETTING: The setting is private practices. MATERIALS AND METHODS: Claims were monitored within one malpractice carrier between 2006 and 2015 covering 10 practices and 184,015 IVF cycles. Total claims, basis of claims, and indemnity paid were evaluated. RESULTS: There were 176 incidents resulting in 30 settled claims with indemnity payments in 21. Categories of claims settled included misdiagnosis (N = 4), lack of informed consent (N = 5), embryology errors (N = 8), and surgical complications (N = 4). Total and average awards were $15,062,000 and $717,238, respectively. Misdiagnosis and lack of informed consent had highest total award amount at $11,583,000 accounting for 76% of award dollars. The two highest awards were $4.5 million and $3.0 million for cancer and genetic misdiagnosis, respectively. Excluding these two awards, payments totaled $7,562,000, ranged from $6000 to $900,000 and averaged $170,363. Errors in handling of embryos were highest in frequency accounting for 38% of claims paid for a total of $1,593,000 with average payment of $199,188. Settlements for surgical complications totaled $1,855,000 and averaged $463,750 per claim. CONCLUSIONS: Misdiagnosis and lack of informed consent are the highest award categories. Embryology lab errors are the most frequent causes of claims with the lowest award per settlement. The average cost for claims settled is relatively high compared to settlements in other specialties.

Current regulatory arrangements for assisted conception treatment in European countries.

Infertility is a condition affecting an increasing number of individuals all over the world. In recent years, this phenomenon has spread across both western countries and developing countries, thus developing the features of a pandemic. For this reason, the World Health Organization (WHO) acknowledged that infertility should be considered a disease to all intents and purposes, as it diminishes the health and wellbeing of the individuals who suffers from it. At present, the most effective means to contain the spread of infertility are essentially prevention and Assisted Reproductive Technologies (ART). With reference to the latter, although most of these techniques are routinely used in the majority of countries, they are still subject to medical, ethical and political debates. There are huge variations noted when the regulatory legislation adopted by different countries to govern infertility treatment in various countries all over the world are reviewed. In fact, it has to be recognized that ART legislation depends on a variety of factors, such as social structure, political choices, ethical issues and religious beliefs. This makes it apparently impossible to create a standard regulation for different countries, especially in case of controversial issues like gamete and embryo donation, embryo cryopreservation or surrogacy.