Predicting in vitro fertilization success in the Brazilian public health system: a machine learning approach.

Infertility has become a global health problem, increasing the number of couples looking for in vitro fertilization (IVF). Despite advances and technical improvements, some couples remain childless due to the high complexity of the technique. The use of machine learning (ML) in the prediction of pregnancy, computing factors that could interfere in the effectiveness of the treatment, is an important tool to optimize these factors and reach the success of pregnancy. The aim of this study was to apply ML models to determine variables related to pregnancy after IVF in a public health service, including pre-implantation variables. This study included 771 women who underwent IVF treatment at Hospital das Clínicas, Federal University of Minas Gerais, between 2013 and 2019. We used the following Machine Learning algorithms: Logistic Regression, Random Forest, XG Boost and Support Vector Machines. The Random Forest algorithm achieved the best performance, with better accuracy, sensitivity and area under the ROC curve to predict the success of IVF evaluated by pregnancy frequency. We also trained a specific model only for women older than 35 years old. Variables in the Random Forest model related to pregnancy after in vitro fertilization.

Resultados en ciclos de FIV-ICSI adicionando hormona luteinizante recombinante a la hormona folículo estimulante recombinante con menotropinas durante la estimulación ovárica en pacientes mayores de 35 años / Results in IVF-ICSI cycles adding luteinizing hormone recombinant to follicle stimulating hormone recombinant with menotropins during ovarian stimulation in patients over 35 years-old

Resumen OBJETIVO Evaluar los resultados en ciclos de FIV-ICSI de dos protocolos de estimulación ovárica en mujeres mayores de 35 años e investigar si agregar hormona luteinizante recombinante a FSH-r en un protocolo de estimulación mejora la respuesta ovárica y, en consecuencia, las tasas de embarazo en este grupo poblacional. MATERIALES Y MÉTODOS Estudio longitudinal, observacional y retrospectivo efectuado en pacientes de la Clínica de Reproducción Hisparep del Hospital Español con diagnóstico de infertilidad, mayores de 35 años, que recibieron un ciclo de hiperestimulación ovárica controlada con FIV-ICSI durante el periodo 2014-2016. El análisis estadístico se efectuó con la prueba de t de Student para muestras independientes. Los estudios se analizaron con el paquete estadístico SPSS IBM, versión 22. RESULTADOS Se analizaron 201 mujeres con infertilidad, mayores de 35 años. El grupo 1 (n = 101) de FIV-ICSI recibió estimulación con hormona folículo estimulante recombinante y hormona luteinizante recombinante 2:1 con menotropinas (Pergoveris® y Merapur®) a partir del segundo día del ciclo. El grupo 2 (n = 100) recibió hormona folículo estimulante recombinante y menotropinas (Gonal F® y Merapur®); en ambos esquemas se utilizó antagonista de GnRH a partir del día 7 del ciclo. La media de ovocitos aspirados fue de 7.5 en el grupo 1 y 9.1 en el grupo 2 (p = 0.058). La media de ovocitos maduros fue 6.2 en el Grupo 1 vs 7.4 en el grupo 2 (p = 0.085). La tasa de fecundación en el grupo 1 fue de 57 vs 67% en el grupo 2 (p = 0.045). En el grupo 1 la tasa de implantación por embrión transferido en fresco fue 24.1 vs 10.3% en el Grupo 2 (p = 0.40), la tasa de recién nacido vivo fue de 30% en el Grupo 1 vs 20.6% en el Grupo 2. La media de embriones vitrificados en el Grupo 1 fue 1.47 vs 1.38 en el Grupo 2. CONCLUSIONES La probable ventaja de la complementación con hormona folículo estimulante recombinante durante la estimulación ovárica en mujeres mayores de 35 años es de interés y se requiere su evaluación en estudios posteriores.

Abstract OBJECTIVE To evaluate the reproductive effects when recombinant luteinizing hormone is added and to compare two stimulation schemes by number of aspirated oocytes, mature oocytes, fertilization and implantation rates, live newborn and number of vitrified embryos. MATERIALS AND METHODS Longitudinal, observational and retrospective study carried out in patients of the Hisparep Reproduction Clinic of the Spanish Hospital with diagnosis of infertility, over 35 years old, who received a controlled ovarian hyperstimulation cycle with IVF-ICSI during the period 2014-2016. The statistical analysis was carried out with the Student t test for independent samples. The studies were analyzed with the IBM SPSS statistical package, version 22. RESULTS We analyzed 201 women with infertility, over 35 years of age. Group 1 (n = 101) of IVF-ICSI received stimulation with recombinant follicle-stimulating hormone and recombinant luteinizing hormone 2: 1 with menotropins (Pergoveris® and Merapur®) from the second day of the cycle. Group 2 (n = 100) received recombinant follicle stimulating hormone and menotropins (Gonal F® and Merapur®); in both schemes, GnRH antagonist was used from day 7 of the cycle. The average number of aspirated oocytes was 7.5 in Group 1 and 9.1 in Group 2 (p = 0.058). Mean mature oocytes were 6.2 in Group 1 vs 7.4 in Group 2 (p = 0.085). The fertilization rate in group 1 was 57 vs. 67% in Group 2 (p = 0.045). In Group 1 the implantation rate per embryo transferred fresh was 24.1 vs 10.3% in Group 2 (p = 0.40), the live newborn rate was 30% in Group 1 vs 20.6% in Group 2. The mean number of vitrified embryos in Group 1 was 1.47 vs 1.38 in Group 2. CONCLUSIONS The probable advantage of supplementation with recombinant follicle-stimulating hormone during ovarian stimulation in women over 35 years of age is of interest and its evaluation is required in subsequent studies.

Avaliação da reserva ovariana na propedêutica da infertilidade / Ovarian reserve evaluation in the propedeutic of infertility

A atenção dada ao potencial reprodutivo diante o envelhecimento ovariano foi realçada pela tendência da mulher moderna de postergar a maternidade e pela procura cada vez maior por serviços de reprodução assistida. Nesse contexto, a avaliação da reserva folicular ovariana surge como tentativa de aferir sua capacidade funcional, melhor aconselhar os casais interessados e nortear protocolos de estimulação, para amenizar encargos emocionais e financeiros de um processo cujos resultados ainda se encontram aquém do desejado. Neste texto, abordam-se a situação atual de marcadores endócrinos basais e dinâmicos e os marcadores ecográficos comuns na avaliação da reserva ovariana em mulheres candidatas a ciclos assistidos.

The attention given to reproductive potential along ovarian ageing process has been enhanced with the trends of modern women to postpone maternity and due to progressive number of couples looking for assisted reproduction treatment. In this context, evaluation of ovarian follicular reserve has been taken into account, with the aim to determine gonadal functional capacity, to afford a better counselling of couples and to coordinate stimulation protocols, diminishing emotional and financial onuses of a complex process with still unsatisfactory results. The scope of this article is to briefly present current situation of basal and dynamic endocrine, and sonographic markers commonly used in ovarian reserve evaluation in candidates for assisted reproductive programs.

Diagnóstico genético pré-implantacional e seu valor prognóstico em tecnologia de reprodução assistida: revisão da literatura / Preimplantation genetic diagnosis and its prognostic value in assisted reproduction technology: literature review

O diagnóstico genético pré-implantacional, associado a técnicas de reprodução assistida como a fertilização in vitro, permite a seleção de pré-embriões euploides para transferência. Nos últimos anos, tem sido indicado visando o aumento nas taxas de sucesso de tratamento, na sua forma de rastreio de aneuploidias para um grupo de pacientes de alto risco reprodutivo como: idade materna avançada, aborto recorrente e falhas repetidas de tratamentos. O objetivo desta revisão é avaliar o valor prognóstico da realização do diagnóstico genético pré-implantação, associado às técnicas de fertilização in vitro e injeção intracitoplasmática de espermatozoide (ICSI), revisar as limitações da técnica e sua eficácia. Embora este grupo com elevado risco reprodutivo apresente alta taxa de aneuploidia, não foram encontrados dados consistentes na literatura a favor da realização do rastreio genético de aneuploidias; portanto, ainda são necessários estudos com grupos mais bem definidos para que o diagnóstico genético pré-implantacional possa ser confirmado como uma ferramenta para aumento de taxas ou como procedimento de rotina, até sua eficácia ser provada.(AU)

The preimplantation genetic diagnosis associated with assisted reproduction technology, as in vitro fertilization, allows selecting euploid pre-embryos for transfer. In recent years, it has been performed as a screening tool for aneuploidy with the purpose of increasing reproductive rates in patient populations at high risk of aneuploidy, such as: advanced maternal age, recurrent pregnancy loss and repeated in vitro fertilization failures. The aim of this review is to evaluate the prognostic value of preimplantation genetic diagnosis, associated with in vitro fertilization and intracytoplasmic sperm injection (ICSI) techniques, to review technology?s limitations and its effectiveness. Although this high risk population group presents high rate of aneuploidy, this review has not shown consistently data in the literature in favor of preimplantation genetic screening; therefore, more studies with well-defined groups are still needed in order that preimplantation genetic diagnosis may be confirmed as a tool for increasing rates or as a routine procedure, until technique?s problems are solved and its effectiveness, proven.(AU)