Corifollitropin Alfa for Controlled Ovarian Stimulation in Assisted Reproductive Technologies: State of the Art / Alfacorifolitropina para estimulação ovariana controlada em tecnologias de reprodução assistida: Estado da arte

Abstract Physical and emotional burdens during the journey of infertile people through assisted reproductive technologies are sufficient to justify the efforts in developing patient-friendly treatment strategies. Thus, shorter duration of ovarian stimulation protocols and the need for less injections may improve adherence, prevent mistakes, and reduce financial costs. Therefore, the sustained follicle-stimulating action of corifollitropin alfa may be the most differentiating pharmacokinetic characteristic among available gonadotropins. In this paper, we gather the evidence on its use, aiming to provide the information needed for considering it as a first choice when a patient-friendly strategy is desired.

Resumo O desgaste físico e emocional durante a jornada de pessoas inférteis pelas tecnologias de reprodução assistida é suficiente para justificar esforços no desenvolvimento de estratégias de tratamento compassivas. Desta forma, a menor duração dos protocolos de estimulação ovariana e a necessidade de menos injeções podem melhorar a adesão, prevenir erros e reduzir custos financeiros. Portanto, a estimulação folicular sustentada da alfacorifolitropina parece ser a característica farmacocinética que melhor a diferencia das gonadotrofinas atualmente disponíveis no mercado. No presente artigo, reunimos evidências sobre seu uso, com o objetivo de fornecer as informações necessárias para considerá-la como primeira escolha quando se deseja uma estratégia amigável ao paciente.

Effect of follicular size on clinical outcomes of frozen-thawed embryo transfer induced by hCG on ovulation in natural cycles / 中华妇产科杂志

Objective:To investigate the effect of follicular size on the clinical outcomes of frozen-thawed embryo transfer induced by human chorionic gonadotropin (hCG) of natural cycles on ovulation.Methods:Clinical data of 427 cycles of frozen-thawed single blastocyst transfer in Nanjing Drum Tower Hospital from January 2016 to December 2019 were retrospectively analyzed. The patients were divided into 15-16 mm group (15≤diameter≤16 mm, n=66), 16-17 mm group (16<diameter≤17 mm, n=101), 17-18 mm group (17<diameter≤18 mm, n=125), 18-20 mm group (18<diameter≤20 mm, n=109),>20 mm group (diameter>20 mm, n=26), according to the maximum follicle diameter on the induction day of hCG ovulation induction. The estradiol and luteinizing hormone (LH) levels, and clinical pregnancy rate, abortion rate and live birth rate were compared in five groups. Results:There were statistically significant differences in estradiol and LH levels among the five groups on the day of hCG induction (all P<0.05). Estradiol levels in 15-16 mm group to >20 mm group gradually increased on the day of hCG induction, and estradiol level in 15-16 mm group was significantly lower than those in 17-18 mm group, 18-20 mm group and >20 mm group (median: 1 002.3 vs 1 103.3 vs 1 171.2 vs 1 539.0 pmol/L), with statistical significances ( P=0.034, P<0.001, P=0.002). On the day of hCG induction, LH levels in 15-16 mm group to >20 mm group showed a decreasing trend, and LH level in 15-16 mm group was significantly higher than those in 17-18 mm group and >20 mm group (median: 37.73 vs 28.24 vs 24.11 U/L), with statistically significant differences ( P=0.007, P=0.006). There were no significant differences in clinical pregnancy rate, abortion rate and live birth rate in 15-16 mm group to >20 mm group (all P>0.05). Conclusion:In the natural cycle protocol of hCG induced ovulation, the small follicle group could achieve similar clinical outcomes compared with normal sized follicles in the single blastocyst transfer of frozen-thawed embryos.

Vaginal Electrical Impedance Detects the Fertile Window in Healthy Women: a Pilot Study / La Impedancia Eléctrica Vaginal Detecta la Ventana Fértil en Mujeres Sanas: un Estudio Piloto

ABSTRACT This work analyzes the electrical impedance (EI) measurement of cervical mucus (CM) using a device to determine the fertile window. In this prospective and longitudinal study, fourteen healthy women aged 18 to 44 were enrolled to evaluate three menstrual cycles. EI was measured through a medical device inserted into the vagina for two minutes daily. Patients were monitored by urine luteinizing hormone (LH) strip, blood collection, and vaginal ultrasound to visualize the dominant follicle. Finally, the predictive EI capacity was validated by the receiver operating characteristic (ROC) of anovulatory vs. ovulatory impedances. The peak of LH was 35.7 (±4.5) mUI/ml and the dominant follicle size was 15.45 mm (±0.559). There were statistical differences in EI measurements between the follicular and luteal phases vs. the ovulation phase (p<0.0361 and p<0.0160). After data normalization, an area under the ROC curve (AUC) of 0.713 (P value= 0.0253), a Youden J index of 0.4545Ω, a sensitivity of 63.6%, and a specificity of 81.8% were found. Low EI in the ovulatory period belongs to the LH ovulatory peak and follicular release. EI can be used for ovulation monitoring, birth control, or promoting pregnancy as a safe and innocuous method.

RESUMEN Este trabajo analiza la medición de la impedancia eléctrica (IE) del moco cervical (MC) mediante un dispositivo para determinar la ventana fértil. En este estudio prospectivo y longitudinal, se incluyeron 14 mujeres sanas de 18 a 44 años para evaluar tres ciclos menstruales. La IE se midió a través de un dispositivo médico colocado en la vagina durante dos minutos diarios. Las pacientes fueron monitoreadas con una tira de hormona luteinizante (LH) en orina, recolección de sangre y ultrasonido vaginal para visualizar el folículo dominante. Finalmente, la capacidad predictiva de IE fue validada por la curva ROC (receiver operating characteristic) de impedancias anovulatorias vs. ovulatorias. El pico de LH fue de 35.7(±4.5) mUI/ml; el folículo de tamaño dominante fue de 15.45 mm (±0.559). Se encontraron diferencias estadísticas para la medición de la IE de las fases folicular y lútea versus la fase de ovulación (p<0.0361 y p<0.0160). Después de la normalización de los datos, se encontró un área bajo la curva ROC (AUC) de 0.713 (valor de P = 0.0253), un índice de Youden J de 0.4545 Ω, sensibilidad del 63.6 % y especificidad del 81.8 %. La IE baja en el período ovulatorio que pertenece al pico ovulatorio de LH y liberación folicular. La IE se puede utilizar para el control de la ovulación, el control de la natalidad o la promoción del embarazo como método seguro e inocuo.

An Experimental Study- to Evaluate the Effect of Shatapushpa Taila on Estrous Phase of Female Wistar Albino Rats

From early adolescence to menopause, the menstrual cycle affects a woman’s physiological and psychological health for about 35 to 40 years in a normal population. Properly functioning hypothalamo pituitary ovarian axis, receptive endometrium with healthy ovum and sperm are considered to be the essential factors for conception. Acharyas have quoted Rutu, Kshetra, Ambhu and Beeja as Garbha sambhava samagri which is essential for conception where in Beeja can be taken as ovum. Shatapusha is mentioned in Kashyapa samhitha as Artavajanaka, hence an effort to evaluate its effect on estrous phase of female Wistar albino rats is the aim of this study. The selected animal was grouped into four groups with 6 animals each. The animal experiment showed significant increase in estrus phase of the oestrous cycle in rats which is the active phase of mating where the female receives the male.

AN OBSERVATIONAL ANALYSIS OF CLINICAL PROFILE ASSOCIATED WITH OVULATION INDUCTION USING LETROZOLE AMONG INFERTILE WOMEN WITH POLYCYSTIC OVARIAN SYNDROME

Background- Polycystic ovary syndrome (PCOS) is major endocrine and metabolic disease in reproductive women. As per latest procedures, letrozole should be taken as the first-line pharmacological treatment for infertile women with PCOS. This study was planned to study the role of clinical profile in ovulation induction after letrozole therapy among infertile women with polycystic ovarian syndrome. This was a prospective analytical observational st Methods- udy carried out at the IVF centre, SMS Medical College, Jaipur. The present study enrolled 100 patients attending the IVF centre for fertility treatment who were diagnosed with PCOS as per Rotterdam criteria. Anthropometric measurements like Body mass index (BMI calculated as weight in kilograms divided by square of height in meters) and waist circumference (the smallest circumference at the level of umbilicus) was taken. A comprehensive physical examination of all patients was done to note signs of clinical hyperandrogenism like acne, alopecia, and hirsutism. Treatment response was defined as ovulation in response to letrozole in doses from 2.5 mg to 7.5 mg. In this study, women from 20 to 25 years of age w Results- ith shorter duration of infertility, lower BMI, lower waist circumference, absence of hirsutism, or mild hirsutism on clinical examination showed better response to Letrozole. ConclusionLetrozole can be considered a suitable ovulation induction agent in infertile PCOS patients with lower BMI, lower waist circumference, and absence of hirsutism. A predictive ovulation score can be developed from basic clinical parameters. Identification of various factors affecting response to letrozole may help the clinician to individualize ovulation induction protocols in PCOS women.

Evaluación de la terapia de reproducción médicamente asistida en 9 años: estudio de cohorte retrospectivo / Medically assisted reproductive therapy assessment in 9 years: retrospective cohort study

OBJETIVO: Describir las tasas de recién nacidos vivos (RNV) y embarazo de la terapia de reproducción médicamente asistida de baja complejidad del Centro de Reproducción Humana de la Universidad de Valparaíso, Chile. MÉTODO: Estudio retrospectivo de todos los ciclos de estimulación ovárica controlada con inseminación intrauterina (IIU) completados, entre los años 2011 y 2019. Se evaluaron las características clínicas basales y los resultados en IIU homólogas y heterólogas según el ciclo inseminado, la causa de infertilidad, el rango etario y el índice de masa corporal (IMC). El desenlace principal fue la tasa de RNV por ciclo inseminado. RESULTADOS: Se estudiaron 1415 ciclos en 700 parejas. La tasa acumulativa de RNV fue del 19,6%, un 18,3% en IIU homóloga y un 39,0% en IIU heteróloga. La tasa de RNV fue del 10,0% al primer ciclo, del 5,8% al segundo ciclo y del 3,7% al tercer o más ciclos. Al separar por IIU heteróloga, esta aumenta al 24,4% al primer ciclo y al 14,6% al segundo ciclo. La tasa de RNV es significativamente mejor en pacientes menores de 35 años (23,7%) y con IMC < 29 (20,8%). CONCLUSIONES: El tratamiento de baja complejidad en pacientes infértiles es una opción terapéutica vigente con una aceptable tasa de RNV por ciclo inseminado. Los resultados están influenciados por la edad y por el IMC.

OBJECTIVE: To describe the rates of live newborns (LNB) and pregnancy of the low complexity therapy of the Centre for Human Reproduction of Universidad de Valparaíso, Chile. METHOD: Retrospective study of all cycles of controlled ovarian stimulation with intrauterine insemination (IUI) completed between 2011-2019. The baseline clinical characteristics and results in homologous and heterologous IUI were evaluated according to inseminated cycle, cause of infertility, age range and body mass index (BMI). The main outcome was rate of LNB per inseminated cycle. RESULTS: 1415 cycles were studied in 700 couples. The cumulative rate of LNB was 19.6%, 18.3% in homologous IUI and 39.0% in heterologous IUI. The LNB rate was 10.0% at the first cycle, 5.8% at the second cycle, 3.7% at the third or more cycles. When separating by heterologous IUI, it increases to 24.4% in the first cycle and 14.6% in the second cycle. The LNB rate is significantly better in patients under 35 years of age (23.7%) and with a BMI less than 29 (20.8%). CONCLUSIONS: Treatment of low complexity in selected infertile patients is a current therapeutic option with an acceptable rate of LNB per inseminated cycle. The results are influenced by age and BMI.

Prevention of Premature Ovulation by Administration of Gonadotropin Releasing Hormone Antagonist the day After Ovulation Triggering in Diminished Ovarian Reserve Patients / Prevenção da ovulação prematura por meio da administração de antagonismo de liberação de gonadotropismo no dia seguinte à ovulação

Abstract Objective The aim of the present retrospective study was to investigate the effectiveness of single-dose gonadotropin releasing hormone (GnRH) antagonist administration, the day after human chorionic gonadotropin (hCG) triggering for final oocyte maturation, on the prevention of premature luteinization in patients with diminished ovarian reserve in in-vitro fertilization (IVF) cycles. The secondary objective of the study was to search the effect of this protocol on pregnancy outcomes. Methods This is a retrospective study including 267 infertile patients who have single antral follicle seen with ultrasonography on the 2nd or 3rd day of the menstrual cycle before starting IVF treatment. We randomized patients into two groups. The case group comprised patients who had single-dose GnRH antagonist injection the day after hCG triggering formed, and the patients who had the standard treatment regime formed the control group. In both groups, the oocytes were collected 36 hours after hCG injection. Results The premature ovulation rate was significantly low in the case group compared with the control group (6.86 versus 20.6% per scheduled cycle) (p=0.022). Also, the oocyte retrieval rate (93.14 versus 67.87% per scheduled cycle) (p=0.013), the oocyte maturity rate (79.42 versus 47.87%) (p=0.041), the fertilization rate (65.68 versus 34.54%) (p=0.018), and the embryo transfer rate per scheduled cycle (44.11 versus 18.78%) (p=0.003) were higher in the GnRH antagonist group than in the control group. Conclusion The administration of GnRH antagonist the day after hCG trigger in IVF treatments of patients with diminished ovarian reserve enabled a significant decrease in the rate of premature ovulation but had no effect on live birth rate.

Resumo Objetivo O objetivo do presente estudo retrospectivo foi investigar a eficácia da administração do antagonista do hormônio liberador da gonadotrofina (GnRH) em dose única no dia seguinte ao desencadeamento da gonadotrofina coriônica humana (hCG) para a maturação final do oócito, na prevenção da luteinização prematura em pacientes com diminuição do ovário reserva em ciclos de fertilização in vitro (FIV). O objetivo secundário do estudo foi pesquisar o efeito deste protocolo nos resultados da gravidez. Métodos Trata-se de um estudo retrospectivo incluindo 267 pacientes inférteis que apresentam um único folículo antral visto por ultrassonografia no 2° ou 3° dia do ciclo menstrual antes de iniciar o tratamento de FIV. Nós randomizamos os pacientes em dois grupos. Os pacientes que receberam injeção de antagonista de GnRH em dose única no dia seguinte ao desencadeamento do hCG formaram o grupo caso, e os pacientes que receberam o regime de tratamento padrão formaram o grupo controle. Em ambos os grupos, os oócitos foram coletados 36 horas após a injeção de hCG. Resultados A taxa de ovulação prematura foi significativamente baixa no grupo caso em comparação com o grupo controle (6,86 versus 20,6% por ciclo programado) (p=0,022). Além disso, a taxa de recuperação de oócitos (93,14 versus 67,87% por ciclo programado) (p=0,013), a taxa de maturidade do oócito (79,42 versus 47,87%) (p=0,041), a taxa de fertilização (65,68 versus 34,54%) (p=0,018) e a taxa de transferência de embriões por ciclo programado (44,11 versus 18,78%) (p=0,003) foram maiores no grupo antagonista de GnRH do que no grupo controle. Conclusão A administração de antagonista de GnRH, no dia seguinte ao desencadeamento de hCG em tratamentos de FIV de pacientes com reserva ovariana diminuída permitiu uma redução significativa na taxa de ovulação precoce,mas não teve efeito na taxa de nascidos vivos.

Application of transabdominal wall press and vaginal B-ultrasound probe to adjust ovarian position in oocyte retrieval / 中国医师杂志

Objective:The aim of this study was to investigate the efficacy and safety of rtansabdominal wall press to adjust ovarian position in patients with difficulty in oocyte retrieval.Methods:A retrospective case-control study was conducted to collect 177 patients with difficulty in oocyte retrieval from January 2020 to December 2021 in the Reproductive Medical Center of Peking University Shenzhen Hospital. Among the 177 patients with difficulty in oocyte retrieval, 76 patients used transabdominal wall press to adjust the position of the ovary (pushing group), and the other 101 patients were treated with routine oocyte retrieval (control group). The oocyte retrieval rate, the number of oocyte and mature oocyte, the number of transferable embryos and high-quality embryos were compared between the two groups, and the incidence of complications was recorded.Results:There was no significant difference between the two groups in the ovarian stimulation program, the dosage of ovulation promoting drugs and the number of follicles ≥14 mm on human chorionic gonadotropin (HCG) day (all P>0.05). The days of promoting ovulation in the pushing group were longer than those in the control group, and the level of estradiol on HCG day was significantly higher than that in the control group (all P<0.05). The rate of oocyte retrieval, the number of oocytes retrieved, the number of transferable embryos and high-quality embryos in the pushing group were significantly higher than those in the control group (all P<0.05). The incidence of complications during oocyte retrieval in the pushing group was significantly lower than that in the control group ( P=0.003). Conclusions:Transabdominal wall press to adjust ovarian position can improve oocyte retrieval rate and reduce the incidence of complications in patients with difficulty in oocyte retrieval.

Relationship between the level of anti Mullerian hormone and antral follicle count and oocytes number in patients undergoing in vitro fertilization / 中国医师杂志

Objective:To investigate the relationship between the level of anti Mullerian hormone (AMH) and antral follicle count (AFC) and oocytes number in patients with in vitro fertilization (IVF). Methods:372 patients with primary infertility who received IVF and embryo transfer (IVF-ET) treatment in the Affiliated Hospital of Guizhou Medical University from January 2020 to December 2020 were prospectively selected as the study subjects. According to the oocytes obtained, the patients were divided into low ovarian response group (LOR group, the number of oocytes obtained ≤5, n=37), normal group (NOR group, the number of oocytes obtained was 6-15, n=292) and high ovarian response group (HOR group, the number of oocytes obtained >15, n=43). The levels of AMH and AFC in the three groups were observed. The relationship between AMH, AFC with LOR and HOR was observed by multivariate logistic analysis. The sensitivity, specificity, optimal cut-off value and area under the curve (AUC) of AMH and AFC for predicting LOR and HOR were calculated by receiver operating characteristic (ROC) curve. Results:There were significant difference in AMH, AFC and oocyte number among the three groups (all P<0.05). The AMH, AFC and oocyte number in NOR group were higher than those in LOR group, and AMH, AFC and oocyte number in HOR group were higher than those in LOR and NOR group (all P<0.05). The results of binary multivariate analysis showed that AFC and AMH were protective factors of LOR (all P<0.05), while AFC and AMH were risk factors of HOR ( P<0.05). The sensitivity and specificity of AMH and AFC in predicting LOR were 83.8% and 75.7%, 65.7% and 84.2%, respectively. The sensitivity of AMH or AFC positive as the standard for predicting LOR was 94.6%, and the specificity of AMH and AFC was 91.6%. The sensitivity and specificity of positive AMH and AFC in predicting HOR were 69.8% and 74.4%, 69.6% and 83.6%, respectively. The sensitivity of AMH or AFC positive as the standard for predicting HOR was 93.0%, and the specificity of AMH and AFC positive as the standard for predicting HOR was 93.0%. Conclusions:AMH and AFC are significantly correlated with oocyte number in patients with primary infertility. Flexible application of AMH and AFC is beneficial to better predict the number of oocytes obtained, which provides a reference for clinical development of individualized ovarian stimulation program.

Association of raised serum progesterone level with ovulation trigger and histology of endometrium in stimulated cycles

Abstract This was a forthcoming study of those patients, who undergo in-vitro fertilization (IVF) and freeze-all embryo, who acquiesce for the study. The number of participated patients (n=350) in this study, underwent for IVF. The blood sample was collected from patients to evaluate the level of serum progesterone in vacuum vials on the day of ovulation trigger. After 36 hrs of ovulation trigger, ovum picked up was done. Quantitative methods were used to estimate the level of serum progesterone through the electrochemiluminescence immunoassay and correlation of serum progesterone with embryo transfer (ET) outcomes. Main outcome of this current study was to evaluate the value of mean serum progesterone level i.e.0.868± 0.712 ng/ml and 0.88±0.723 ng/ml was found in case of pregnancy positive and negative respectively, at p=0.216 value. In antagonist (n=40) and agonist (n=310) cases, it was 8(20%) and 37(11.94%) PL occurrence was noted at p=0.143 respectively. An overall value of the premature lutenization (PL) occurrences was 13.63% and 15.25% observed in both positive and negative cases of pregnancy at p=0.216 respectively. This study concluded that 12.66% of PL occurrences were recorded in the case of IVF. Study results proved, there were no significant effect of PL on pregnancy outcomes.

Analysis of related factors and prediction of poor ovarian response in patients with controlled ovarian stimulation / 中华妇产科杂志

Objective:To explore the related factors of poor ovarian response (POR) in patients receiving controlled ovarian stimulation (COS) and to establish the nomogram for predicting POR in patients who received in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI).Methods:In this retrospective research, clinical data of 17 164 cycles of patients who received IVF/ICSI treatment at Henan Provincial People′s Hospital from September 1st, 2016 to September 1st, 2020 were analyzed. Independent correlative factors affecting the occurrence of POR were screened by logistic regression, which were the model enrollment variables in the prediction model. Totally 13 266 cycles with well-record of enrollment variables were screened, and these data were randomly divided into model group (9 896 patients) and validation group (3 370 patients) according to 3∶1. The nomogram was established according to the regression coefficient of the relevant variables. The prediction accuracy of the nomogram was evaluated by calculating area under the receiver operating characteristic curve (AUC).Results:Multivariate logistic regression analysis showed age, infertility type, body mass index, anti-Müllerian hormone, basal follicle stimulating hormone, basal estrogen, antral follicle number, previous times of POR, history of ovarian surgery, ovulation stimulation protocol and average amount of gonadotropin were independent correlative factors affecting the occurrence of POR (all P<0.05). In the model group, according to the above factors, the prediction model and nomogram of POR risk were constructed and the validation group verified the model. The AUC of the model group was 0.893 (95% CI: 0.885-0.900), and the AUC of the validation group was 0.890 (95% CI: 0.878-0.903). Conclusion:The influencing factors of POR after COS in patients treated by IVF/ICSI are screened, and the nomogram for predicting POR established in this study is proved to be effective, simple, intuitive and clear in predicting the occurrence of POR.

Effects of letrozole combined with human menopausal gonadotropin on pregnancy rate and prognosis in patients with refractory polycystic ovary syndrome / 中国基层医药

Objective:To investigate the effects of letrozole combined with human menopausal gonadotropin (HMG) on pregnancy rate and prognosis in patients with refractory polycystic ovary syndrome (PCOS).Methods:A total of 102 patients with refractory PCOS who received treatment in Jinhua Hongyue Women's and Children's Hospital between May 2019 and May 2020 were included in this study. They were randomly assigned to observation and control groups ( n = 51/group). All patients received the same treatment in the early period. During later ovulation induction period, patients in the control group were administered HMG and those in the observation group were given letrozole combined with HMG. Before treatment and 3 months after treatment, sex hormones [follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E 2), testosterone (T)], arterial hemodynamic indicators around the follicle [end diastolic velocity (EDV), peak systolic velocity (PSV), pulsation index (PI)], endometrial thickness and classification were compared between the two groups. The ovulation rate and pregnancy rate as well as pregnancy outcomes at 6 months of follow-up were recorded in each group. Results:After 3 months of treatment, FSH, LH, E 2 and T levels in each group were significantly decreased compared with those before treatment (all P < 0.05). FSH, LH, E 2 and T levels in the observation group were (1.85 ± 0.45) U/L, (9.86 ± 1.47) U/L, (81.25 ± 10.47) pmol/L, (1.75 ± 0.26) nmol/L, respectively, which were significantly lower than those in the control group [(3.12 ± 1.47) U/L, (12.58 ± 2.14) U/L, (109.25 ± 27.14) pmol/L, (3.58 ± 0.76) nmol/L, t = 5.90, 7.48, 6.87, 16.27, all P < 0.05). EDV in each group was significantly decreased after 3 months of treatment compared with that before treatment (both P < 0.05). After treatment, EDV in the observation group was significantly lower than that in the control group [(3.12 ± 1.42) cm/s vs. (5.14 ± 1.89) cm/s, t = 21.14, P < 0.001]. PSV in each group was significantly increased after treatment compared with that before treatment (both P < 0.05). After treatment, PSV in the observation group was significantly higher than that in the control group [(13.36 ± 2.01) cm/s vs. (10.24 ± 2.47) cm/s, t = 4.21, P < 0.001]. In each group, PI measured after treatment was not significantly different from that measured before treatment (both P > 0.05). After treatment, endometrial thickness in the observation group was significantly higher than that in the control group [(9.09 ± 1.58) mm vs. (8.41 ± 1.42) mm, t = 2.28, P < 0.05]. Ovulation rate in the observation group was significantly higher than that in the control group [88.24% (45/51) vs. 70.59% (36/51), χ2 = 4.85, P < 0.05]. There were no significant differences in endometrial type, biochemical pregnancy, clinical pregnancy rate, abortion rate, and premature delivery rate between the two groups (all P > 0.05). Conclusion:Letrozole combined with HMG has an ideal effect on refractory PCOS. It can improve the levels of sex hormones, restore the hemodynamic status in ovarian stroma and increase ovulation rate.

Pre-sincronización con Progesterona para la Inducción de Ciclicidad en Vacas Bos taurus indicus en Periodo de Anestro Posparto / Presynchronization with Progesterone for Induction of Cyclicity in Bos Taurus Indicus Cows in Postpartum Anestrus Period / Pré-sincronização com Progesterona para a Indução de Ciclicidade em Vacas Bos Taurus Indicus em Período de Anestro Pós-Parto

Resumen Objetivo. Este trabajo tuvo como objetivo evaluar el efecto de la pre-sincronización con progesterona (P4) por 3 y 6 días en vacas de raza Nelore en periodo de anestro posparto, sometidas a un programa de inseminación artificial a tiempo fijo (IATF). Materiales y métodos: Fueron utilizadas 74 vacas multíparas de raza Nelore con estado de condición corporal de 2,5. Las vacas fueron sometidas a tres grupos experimentales, grupo control y grupos pre-sincronizados con P4 por un periodo de 3 y 6 días. Para la determinación del estado de anestro posparto, fueron realizadas ecografías y toma de muestras de sangre con la finalidad de verificar la ausencia de P4 endógena. Cuarenta y cinco días después de la IA fue realizado el diagnóstico de la gestación. Los datos fueron obtenidos por análisis descriptivo y en el caso de presentación de diferencias significativas fue utilizado la prueba de Chi-cuadrado, considerándose una frecuencia de P< 0,05. Resultados: Fue observada mayor tasa de gestación para el grupo que fue pre-sincronizado por tres días con P4 (40 %), con relación a los grupos de seis días de pre-sincronización y control (25 % y 32 %, respectivamente). Conclusión: Es posible concluir que la pre-sincronización con P4 por tres días, mejoró la tasa de gestación de vacas de raza Nelore en periodo de anestro posparto.

Abstract Objective: The objective of this study was to evaluate the effect of pre-synchronization with progesterone (P4) for 3 and 6 days in Nelore cows in postpartum anestrus period, submitted to a fixed-time artificial insemination program (FTAI). Materials and methods: Seventy-four multiparous Nelore cows with a body condition of 2.5 were used. The cows were submitted to three experimental groups, control group and groups pre-synchronized with P4 for a period of 3 and 6 days. For the determination of postpartum anestrus status, ultrasound scans and blood samples were taken to verify the absence of endogenous P4. Forty-five days after AI, gestation was diagnosed. Data were obtained by descriptive analysis and in the case of presentation of significant differences the Chi-square test was used, considering a frequency of P < 0.05. Results: A higher gestation rate was observed for the group that was pre-synchronized for three days with P4 (40 %), in relation to the groups of six days of pre-synchronization and control (25 % and 32 %, respectively). Conclusion: It is possible to conclude that the pre-synchronization with P4 for three days improved the gestation rate of Nelore cows in the postpartum anestrus period.

Resumo Objetivo: O objetivo deste estudo foi avaliar o efeito da pré-sincronização com progesterona (P4) durante 3 e 6 dias em vacas de raça Nelore em período de anestro pós-parto, submetidas a um programa de inseminação artificial em tempo fixo (IATF). Materiais e métodos: Foram utilizadas 74 vacas multíparas da raça Nelore com estado de condição corporal de 2,5. As vacas foram submetidas a três grupos experimentais, grupo controle e grupos pré-sincronizados com P4 por um período de 3 e 6 dias. Para a determinação do estado de anestro pós-parto, foram realizadas ultrassonografias e coleta de amostras de sangue com a finalidade de verificar a ausência de P4 endógena. Quarenta e cinco dias após a IA foi realizado o diagnostico da gestação. Os dados foram obtidos por análise descritiva e no caso de diferenças significativas foi utilizado o teste do Quí-quadrado, considerando-se uma freqüência de P < 0,05. Resultados: Foi observada maior taxa de gestação para o grupo que foi pré-sincronizado por três dias com P4 (40 %), com relação aos grupos de seis dias de pré-sincronização e controle (25 % e 32 %, respetivamente). Conclusão: É possível concluir que a pré-sincronização com P4 por três dias, melhorou a taxa de gestação de vacas Nelore em período de anestro pós-parto.

Intravaginal progesterone device (1. 9g) and estradiol benzoate for follicular control in the mare during spring and summer / [Implante intravaginal de progesterona (1, 9g) e benzoato de estradiol no controle folicular de éguas durante a primavera e o verão]

The objective of this study was to evaluate follicular growth and ovulatory rates in mares treated with an intravaginal progesterone device (P4) during the 10-day period, associated with the use of estradiol benzoate (EB). The results were compared during the transition period (ET) in the spring and the breeding season in the summer (ER). The variables were submitted to ANOVA (Tukey's test), considering P<0.05. No ovulation occurred during the permanence of the P4 implant in both experimental periods. The ovulatory rate in the ER was 100% (n = 8) and in the ET 62.5% (n = 5; P = 0.0547). Significant differences were observed (<0.001), in both periods, comparing follicular growth rates during the permanence of P4 device (ER: 1.33 ± 0.89mm/d; ET: 1.00 ± 0.81mm/d) to the period without P4 (ER: 3.63 ± 1.33 mm/d; ET: 3.31 ± 1.66 mm/d). The present study demonstrated applicability and efficiency of a hormonal protocol using P4 intravaginal device and EB for follicular control in mares, both during ET and ER.

O objetivo deste trabalho foi avaliar a taxa de crescimento folicular e a taxa ovulatória em éguas tratadas com dispositivo intravaginal de progesterona (P4) durante o período de 10 dias, associado à utilização de benzoato de estradiol (BE). Os resultados foram comparados durante o período de transição (ET) da primavera com a época de reprodução no verão (ER). As variáveis foram submetidas à ANOVA (teste de Tukey), considerando-se P<0,05. Nenhuma ovulação ocorreu durante a permanência do dispositivo de P4 em ambos os períodos experimentais. A taxa ovulatória na ER foi de 100% (n = 8) e na ET, de 62,5% (n=5; P=0,0547). Diferença significativas (<0,001) foram observadas, em ambos os períodos experimentais, comparando as taxas de crescimento folicular durante a permanência da P4 (ER: 1,33 ± 0,89mm/d; ET: 1,00 ± 0,81mm/d) com o período sem P4 (ER: 3,63 ± 1,33mm/d; ET: 3,31 ± 1,66mm/d). O presente estudo demonstrou aplicabilidade e eficiência do protocolo hormonal utilizando dispositivo intravaginal de P4 e BE para controle folicular de éguas, tanto na ET quanto na ER.

Método de Ovulação Billings: entre eficácia e desconhecimento / Billings Ovulation Method: between efficacy and lack of knowledge / Método de Ovulación Billings: entre la eficacia y el desconocimiento

Resumo Apesar dos grandes investimentos, os métodos artificiais de planejamento familiar ainda apresentam limitações. Desde a década de 1950, cientistas trabalham para desenvolver um método natural confiável. Este artigo revisa a literatura sobre o Método de Ovulação Billings, apontando sua lógica, sua eficácia, seus benefícios, seus desafios e suas regras. Trata-se de método natural, embasado em mais de cinquenta anos de pesquisas. Sua chave de leitura é o muco cervical, confiável indicador da fertilidade, e sua eficácia está entre 97% e 99%, comparável aos métodos mais eficazes. O método também é indicado para todo tipo de ciclo, pois não se baseia em cálculos, e sim na observação do muco. Conclui-se que no Brasil é preciso fortalecer programas que ofereçam educação sexual mais global à população, capacitando ainda profissionais da saúde a respeito dos métodos naturais de planejamento familiar.

Abstract Despite large investments, artificial family planning methods still have limitations. Since the 1950s, scientists have worked to develop a reliable natural method. This article reviews the literature on the Billings Ovulation Method, pointing out its logic, efficacy, benefits, challenges, and rules. It is a natural method, based on more than fifty years of research. Its reading key is the cervical mucus, a reliable indicator of fertility, and its efficacy is between 97 and 99%, comparable to most effective methods. Billings is also suitable for all types of cycles, as it is not based on calculations, but on the observation of the mucus. In conclusion, Brazil needs to strengthen programs that offer more global sexual education to the population, also training health professionals on natural family planning methods.

Resumen A pesar de las grandes inversiones, los métodos artificiales de planificación familiar todavía tienen limitaciones. Desde la década de 1950, los científicos vienen trabajando para desarrollar un método natural confiable. Este artículo revisa la literatura sobre el Método de Ovulación Billings, presentando su lógica, efectividad, beneficios, desafíos y reglas. Se trata de un método natural, basado en más de cincuenta años de investigación. Su clave es el moco cervical, un indicador confiable de fertilidad, y su efectividad está entre el 97% y el 99%, comparable a los métodos más efectivos. El Método de Ovulación Billings también es adecuado para todo tipo de ciclos, ya que no se fundamenta en cálculos, sino en la observación de mocos. Se concluye que en Brasil es necesario fortalecer programas que ofrezcan una educación sexual más global a la población, además de capacitar a los profesionales de la salud sobre métodos naturales de planificación familiar.

Pleuropatía secundaria a inductores de la ovulación / Pleuropathy secondary to ovulation inducers

Introducción: Se denomina derrame pleural al acúmulo de líquido en el espacio pleural por encima de 5 y 15 mL en un hemitórax. Diferentes etiologías son las responsables de su aparición, pero un grupo estas están dadas por la etiología medicamentosa. El síndrome de hiperestimulación ovárica constituye una complicación secundaria al uso de la terapia con inductores de la ovulación. Es poco conocida en la literatura médica la asociación del tratamiento con inductores de la ovulación en la génesis del derrame pleural. Objetivo: Revisar los aspectos clínico-fisiopatológicos más importantes reportados sobre la pleuresía en el síndrome de hiperestimulación ovárica. Desarrollo: Se realizó una revisión a propósito de un caso clínico de una paciente de 34 años de edad con antecedentes de salud, seguida en consulta de fertilidad, a la cual se le aplicó tratamiento con citrato de clomifeno y desarrolló un síndrome de hiperestimulación ovárica moderado e inmediato, cuya expresión clínica fue un derrame pleural derecho de moderada cuantía. La pleuresía es poco frecuente, depende de la predisposición genética individual de la paciente y la susceptibilidad a los medicamentos; la incidencia varía entre 0,6 y 10 por ciento. Se han descrito diferentes factores de riesgo de presentarlo, aunque cualquier mujer sometida a estos tratamientos lo puede desarrollar. El tratamiento es sintomático restituyendo el volumen intravascular con la administración de cristaloides y/o albúmina. Conclusiones: La asociación del síndrome de hiperestimulación ovárica y la pleuropatía secundaria al tratamiento con citrato de clomifeno no es frecuente(AU)

Introduction: Pleural effusion is called the accumulation of fluid in the pleural space above 5 and 15 mL in a hemithorax. Different etiologies are responsible for its appearance but a group of them are given by drug etiology. Ovarian hyperstimulation syndrome is a secondary complication to the use of ovulation inducer therapy. The association of treatment with ovulation inducers in the genesis of pleural effusion is little known in the medical literature. Objective: To review the most important clinical-pathophysiological aspects reported on pleurisy in ovarian hyperstimulation syndrome. Methods: A review was carried out on the purpose of a clinical case of a 34-year-old patient with a medical history, followed in a fertility consultation. She was treated with clomiphene citrate and she developed an immediate moderate ovarian hyperstimulation syndrome. The clinical expression was a moderate right pleural effusion. Pleurisy is rare. It depends on the individual genetic predisposition of the patient and the susceptibility to drugs; the incidence varies between 0.6 and 10 percent. Different risk factors have been described, although any woman subjected to these treatments can develop it. Treatment is symptomatic, restoring the intravascular volume with the administration of crystalloids and / or albumin. Conclusions: The association of ovarian hyperstimulation syndrome and pleuropathy secondary to treatment with clomiphene citrate is not frequent(AU)

Prostaglandin E2 induces ovulation in prepubertal mice / Prostaglandina E2 induz ovulação em camundongos pré-púberes

The objective of this study was to determine the ability of prostaglandin E2 (PGE2) to induce ovulation and expression of PGE2 receptor (EP2 and EP4) and COX genes (COX-1 and COX-2) in the ovary and pituitary of prepubertal mice. The positive control consisted of the application of 5 µg of gonadotropin-releasing hormone (GnRH, n = 29); the negative control applied 0.5 mL of phosphate buffered saline (PBS, n=31); the treatment tested the application of 250 µg of PGE2 (n = 29), making a total of 89 prepubertal mice (BALB/c). Mice were euthanized 14 to 15 h after treatments to detect ovulation and tissue collection. A Chi-square test was used to compare the proportion of animals ovulating. Gene expressions and number of ovulation were analyzed by one-way ANOVA and Tukey's test was used to compare means among groups. A greater proportion of mice (P < 0.001) ovulated after receiving GnRH (89.7%, 26/29) compared to PGE2 group (58.6%, 17/29). However, the proportion was higher compared to those treated with PBS (0%, 0/31). Ep2gene expression in the pituitary was > two-fold higher (P < 0.05) in the PGE2 group compared to the PBS and GnRH groups. Further, PGE2 stimulated Cox1 (2.7 fold, P < 0.05) while GnRH stimulated Cox2 expression (6.5 fold, P < 0.05) in the pituitary when compared to the PBS group. In conclusion, our results support the hypothesis that PGE2 can induce ovulation in prepubertal mice with a concomitant increase in Ep2 and Cox1 gene expression in the pituitary gland.(AU)

O objetivo deste estudo foi determinar a capacidade da prostaglandina E2 (PGE2) em induzir a ovulação e expressão do receptor PGE2 (EP2 e EP4) e genes COX (COX-1 e COX-2) no ovário e na hipófise de camundongos pré-púberes. O controle positivo consistiu na aplicação de 5 µg de hormônio liberador de gonadotrofina (GnRH, n = 29); o controle negativo aplicação 0,5 mL de tampão fosfato-salino (PBS, n=31); o tratamento testado aplicação de 250 µg de PGE2 (n = 29), perfazendo um total de 89 camundongos (BALB/c) pré-púberes. Os camundongos foram sacrificados 14 a 15 h após os tratamentos para detectar ovulações e coleta de tecido. O teste do qui-quadrado foi usado para comparar a proporção de animais ovulando. As expressões gênicas e o número de ovulação foram analisados por ANOVA e o teste de tukey foi usado para comparar as médias entre os grupos. Uma maior proporção de camundongos (P <0,001) ovulou após receber GnRH (89,7%, 26/29) em comparação com o grupo PGE2 (58,6%, 17/29). No entanto, a proporção foi maior em comparação com aqueles tratados com PBS (0%, 0/31). A expressão do gene Ep2 na hipófise foi duas vezes maior (P <0,05) no grupo PGE2 em comparação com os grupos PBS e GnRH. Além disso, a PGE2 estimulou a Cox1(2,7 vezes, P <0,05) enquanto o GnRH estimulou a expressão de Cox2 (6,5 vezes, P <0,05) na pituitária em comparação com o grupo PBS. Em conclusão, nossos resultados suportam a hipótese de que PGE2 é capaz de induzir ovulação em camundongos pré-púberes com aumento concomitante na expressão dos genes Ep2 e Cox1 na glândula pituitária.(AU)

Atualizações na terapêutica farmacológica para infertilidade na mulher diagnosticada com síndrome de ovários policísticos: revisão de literatura / Updates on pharmacological treatments for infertility in women diagnosed with polycystic ovary syndrome: a literature review

Objetivo: Abordar atualizações referentes à terapia medicamentosa para indução da ovulação nas mulheres diagnosticadas com síndrome dos ovários policísticos (SOP). Métodos: Revisão de literatura por meio de levantamento bibliográfico do período de 1975 a 2021, nas bases eletrônicas PubMed, SciELO e MedLine, complementado pela Diretriz Internacional Baseada em Evidências para a Avaliação e Manejo da SOP de 2018 e pelo manual da Febrasgo para SOP. Sete descritores que atendessem à finalidade da pesquisa foram utilizados. Resultados: A literatura aponta atualmente algumas drogas como opção na terapêutica para a indução de ovulação, como metformina, letrozol e citrato de clomifeno, evidenciando que o uso de letrozol isolado e em associação com a metformina apresentaram melhores taxas de ovulação, 71,5% e 75,4%, respectivamente. Conclusão: O uso do letrozol isolado ou combinado com a metformina apresentou os melhores resultados nas taxas de gravidez e ovulação, todavia o tratamento para indução ovulatória deve ser individualizado.(AU)

Objective: To address updates of medicinal therapy for ovulation induction in women diagnosed with polycystic ovary syndrome (PCOS). Methods: Reviewing Literature through a bibliographic survey from 1975 to 2021, on the electronic databases PubMed, SciELO and MedLine, complemented by the International Evidence-Based Guideline for the Evaluation and Management of PCOS 2018 and the Febrasgo guide for PCOS. Seven descriptors that matched to the purpose of the research were applied. Results: Some drugs are currently indicated in the literature as an option for ovulation induction therapy, such as: metformin, letrozole and clomiphene citrate, showing that the use of letrozole alone and in association with metformin had better ovulation rates, 71.5% and 75.4%, respectively. Conclusion: The use of letrozole alone or combined with metformin showed the best results in pregnancy and ovulation rates, however, treatment for ovulatory induction must be individualized.(AU)

Freeze-all policy for in vitro fertilization in women with normal response to ovarian stimulation / Congelamento de todos os embriões em ciclos de fertilização in vitro em mulheres com resposta normal à estimulação ovariana

ABSTRACT Objective To answer the question if the freeze-all strategy and subsequent frozen embryo transfer is preferable to fresh embryo transfer for patients with normal response to ovarian stimulation (4 to 15 oocytes recovered) during in vitro fertilization treatments. Methods A retrospective cohort from two human reproduction centers between 2013 and 2017. A total of 471 frozen embryo transfers from freeze-all cycles, and 3,208 fresh transfers were included. Results After propensity score matching adjustment for age and number of eggs, 467 freeze-all cycles and 934 fresh cycles were analyzed, revealing no statistically significant difference between groups in relation to clinical pregnancy rate (32.5% in the Freeze-all Group and 32.3% in the Fresh Group, p=0.936). For women aged 40 years and older, we observed a statistically significant higher clinical pregnancy rate when freeze-all strategy was used (29.3% in the Freeze-all Group and 19.8% in the Fresh Group, p=0.04). Conclusion Freeze-all strategy was not superior to fresh transfer for all patients with normal response to ovarian stimulation. However, women aged 40 years and older could benefit from this strategy. This deserves further investigation in future research, preferable in a prospective randomized study.

RESUMO Objetivo Responder à pergunta se a estratégia freeze-all (congelamento de todos os embriões) e subsequente transferência de embriões congelados é preferível à transferência de embriões a fresco em pacientes com resposta normal à estimulação ovariana (4 a 15 ovócitos coletados) durante tratamentos de fertilização in vitro . Métodos Coorte retrospectiva de dois centros de reprodução humana entre 2013 e 2017. No total, foram incluídas 471 transferências de ciclos com congelamento de todos os embriões, e 3.208 transferências a fresco. Resultados Após o ajuste do escore de propensão para idade e número de óvulos, foram analisados 467 ciclos com congelamento de todos os embriões e 934 ciclos a fresco, não havendo diferença estatisticamente significativa entre os grupos em relação à taxa de gravidez clínica (32,5% no Grupo Freeze-all e 32,3% no Grupo a Fresco, p=0,936). Para mulheres com 40 anos ou mais, observamos uma taxa de gravidez clínica estatisticamente maior quando foi utilizada a estratégia freeze-all (29,3% no Grupo Freeze-all e 19,8% no Grupo a Fresco, p=0,04). Conclusão A estratégia freeze-all não foi superior à transferência a fresco para todas as pacientes com resposta normal à estimulação ovariana. No entanto, mulheres com 40 anos ou mais podem ter algum benefício com essa estratégia. Isso justifica uma investigação mais aprofundada em pesquisas futuras e, de preferência, em estudos prospectivos randomizados.

Fertility preservation in breast cancer with oral progestin: is it an option? A pilot study / Preservação da fertilidade com progestágeno oral em pacientes com câncer de mama: é uma opção? Estudo-piloto

ABSTRACT Objective To compare the effectiveness of oral progestins and injectable gonadotropin-releasing hormone antagonist medication in cancer fertility preservation in patients with breast cancer. Methods A cross-sectional study with 40 breast cancer patients submitted to cancer fertility preservation, who were divided into two groups according to histochemical analysis of progesterone receptors to define luteinizing hormone block: if positive, use of gonadotropin-releasing hormone antagonist, if negative, use of oral progestins. The mean age, medication days, antral follicle count, number of oocytes in metaphase II and the occurrence of ovarian hyperstimulation syndrome were compared. Results A total of 20 patients both in the group using gonadotropin-releasing hormone antagonist, and in the group with oral progestins, respectively, had a mean age of 33.9 (32-35.8) and 33.8 (32-35.6) years; days of medications of 11 (9.7-12.3) and 12.8 (11.6-13.9), p=0.037; antral follicle count of 9 (7.11-12) and 8.5 (6-11.9), p=0.370; metaphase II oocyte number of 4 (2.1-9.8) and 7.5 (3.1-10), p=0.348; and ovarian hyperstimulation syndrome of 2 (10%) and 5 (25%) cases, p=0.212. Conclusion The use of oral progestins, in spite of requiring longer treatment time, is effective in relation to the protocol with gonadotropin-releasing hormone antagonist, and offers greater comfort at a lower cost in breast cancer patients with negative progesterone receptors, submitted to cancer fertility preservation.

RESUMO Objetivo Comparar a efetividade dos progestágenos orais em relação à medicação injetável antagonista de hormônio liberador de gonadotrofina na preservação da fertilidade oncológica de pacientes com câncer de mama. Métodos Estudo transversal com 40 pacientes com câncer de mama submetidas à preservação da fertilidade oncológica, que foram divididas em dois grupos, conforme análise histoquímica dos receptores de progesterona, para definir o bloqueio de hormônio luteinizante: se positivos, uso de antagonista de hormônio liberador de gonadotrofina; se negativos, uso de progestágenos orais. Comparou-se média de idade, dias de medicações, contagem de folículos antrais, número de oócitos em metáfase II e ocorrência de síndrome do hiperestímulo ovariano. Resultados Vinte pacientes, tanto no grupo com uso de antagonista de hormônio liberador de gonadotrofina, quanto no grupo com progestágenos orais, respectivamente, apresentaram média de idade de 33,9 (32-35,8) e 33,8 (32-35,6) anos; 11 (9,7-12,3) e 12,8 (11,6-13,9) de dias de medicações com p=0,037; contagem de folículos antrais de 9 (7,11-12) e 8,5 (6-11,9), com p=0,370; número de oócitos metáfase II de 4 (2,1-9,8) e 7,5 (3,1-10), com p=0,348, e síndrome do hiperestímulo ovariano de 2 casos (10%) e 5 casos (25%), com p=0,212. Conclusão O uso de progestágenos orais, apesar de necessitar de maior tempo de tratamento, é efetivo em relação ao protocolo com antagonista de hormônio liberador de gonadotrofina e oferece maior conforto com menor custo em pacientes com câncer de mama com receptores de progesterona negativos, submetidas à preservação da fertilidade oncológica.