Estimulación ovárica en síndrome de Mayer-Rokitansky: reporte de caso y revisión de la literatura / Controlled ovarian stimulation in Mayer-Rokitansky syndrome: case report and literature review

Resumen El síndrome de Mayer-Rokitansky-Küster-Hauser (SMRKH) es una anomalía del tracto genital femenino caracterizada por ausencia congénita del útero y porción superior de la vagina. Ocurre en uno de cada 4,500 nacimientos y se diagnostica normalmente durante la adolescencia al presentarse amenorrea primaria. Su función ovárica está preservada, pero la información actual respecto al potencial reproductivo de estas pacientes es limitada. Se presenta el caso de una mujer con diagnóstico de SMRKH sometida a estimulación ovárica para transferencia de embriones a útero subrogado y se discute su potencial reproductivo: técnicas de reproducción asistida, intervenciones e impacto psicológico.

Abstract Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) is a congenital anomaly of the female genital tract characterized by congenital absence of the uterus and upper part of the vagina. It occurs in 4,500 female births and diagnosis is usually made during adolescence when primary amenorrhea presents. They have functioning ovaries but data regarding their reproductive potential is limited. We hereby report the case of a woman diagnosed with MRKH syndrome in whom assisted reproductive techniques were used to try to achieve pregnancy by gestational surrogacy and their reproductive potential is discussed: assisted reproductive techniques, procedures, and psychological impact.

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.

Improving Implantation Rate in 2nd ICSI Cycle through Ovarian Stimulation with FSH and LH in GNRH Antagonist Regimen / Melhorando a taxa de implantação no 2° ciclo de ICSI através do estímulo ovariano com FSH e LH no regime com antagonista do GnRH

Abstract Objective To investigate whether patients with a previous recombinant follicle stimulating hormone (rFSH)-stimulated cycle would have improved outcomes with rFSH + recombinant luteinizing hormone (rLH) stimulation in the following cycle. Methods For the present retrospective case-control study, 228 cycles performed in 114 patients undergoing intracytoplasmic sperm injection (ICSI) between 2015 and 2018 in an in vitro fertilization (IVF) center were evaluated. Controlled ovarian stimulation (COS) was achieved with rFSH (Gonal-f, Serono, Geneva, Switzerland) in the first ICSI cycle (rFSH group), and with rFSH and rLH (Pergoveris, Merck Serono S.p.A, Bari, Italy) in the second cycle (rFSH + rLH group). The ICSI outcomes were compared among the groups. Results Higher estradiol levels, oocyte yield, day-3 high-quality embryos rate and implantation rate, and a lower miscarriage rate were observed in the rFSH + rLH group compared with the rFSH group. In patients < 35 years old, the implantation rate was higher in the rFSH + rLH group compared with the rFSH group. In patients ≥ 35 years old, higher estradiol levels, oocyte yield, day-3 high-quality embryos rate, and implantation rate were observed in the rFSH + rLH group. In patients with ≤ 4 retrieved oocytes, oocyte yield, mature oocytes rate, normal cleavage speed, implantation rate, and miscarriage rate were improved in the rFSH + rLH group. In patients with ≥ 5 retrieved oocytes, higher estradiol levels, oocyte yield, and implantation rate were observed in the rFSH + rLH group. Conclusion Ovarian stimulation with luteinizing hormone (LH) supplementation results in higher implantation rates, independent of maternal age and response to COS when compared with previous cycles stimulated with rFSH only. Improvements were also observed for ICSI outcomes and miscarriage after stratification by age and retrieved oocytes.

Resumo Objetivo: Investigar se há algum efeito da suplementação com hormônio luteinizante (LH, na sigla em inglês) no regime com antagonista do hormônio liberador de gonadotropina (GnRH, na sigla em inglês) sobre os resultados dos ciclos consecutivos de injeção intracitoplasmática de espermatozoides (ICSI, na sigla em inglês). Métodos Para o presente estudo retrospectivo de caso-controle, foram avaliados 228 ciclos de microinjeção intracitoplasmática de espermatozoides (ICSI, na sigla em inglês) realizados em 114 pacientes entre 2015 e 2018 em um centro privado de fertilização in vitro (FIV) afiliado a uma universidade. O estímulo ovariano controlado (EOC) foi feito com hormônio folículo- estimulante recombinante (rFSH, na sigla em inglês) (Gonal-f, Serono, Genebra, Suíça) no primeiro ciclo de ICSI (grupo rFSH), e com rFSH e rLH (Pergoveris, Merck Serono S.p.A, Bari, Itália) no segundo ciclo (grupo rFSH + rLH). Os desfechos dos ciclos de ICSI foram comparados entre os grupos. Resultados Níveis mais elevados de estradiol, de recuperação oocitária, taxa de embriões de alta qualidade no 3° dia e taxa de implantação, e menor taxa de aborto foram observados no grupo rFSH + rLH. Em pacientes < 35 anos, a taxa de implantação foi maior no grupo rFSH + rLH em comparação com o grupo rFSH. Em pacientes com ≥ 35 anos, maiores níveis de estradiol, recuperação oocitária, a taxa de embriões de alta qualidade no 3° dia e a taxa de implantação foram observados no grupo rFSH + rLH. Em pacientes com baixa resposta ao EOC (≤ 4 oócitos recuperados), a recuperação oocitária, a taxa de oócitos maduros, a taxa de velocidade normal de clivagem, a taxa de implantação e a taxa de aborto foram melhoradas no grupo rFSH + rLH. Em pacientes com resposta normal ao EOC (≥ 5 oócitos recuperados), níveis mais elevados de estradiol, recuperação oocitária e taxa de implantação foram observados no grupo rFSH + rLH. Conclusão A estimulação ovariana com suplementação de LH resultou em taxas de implantação mais altas, independentemente da idade materna e da resposta ao EOC, em comparação com os ciclos anteriores estimulados apenas com rFSH. Melhorias também foram observadas nos resultados da ICSI e na taxa de aborto quando as pacientes foram estratificadas por idade e número de oócitos recuperados.

Pasado presente y futuro de la estimulación ovárica en el tratamiento de la infertilidad / Past, present and future of ovarian stimulation in infertility treatment

La mejor comprensión de la fisiología reproductiva y la disponibilidad de más y mejores recursos diagnóstico/terapéuticos permiten individualizar la estimulación ovárica y hacerla más efectiva (mejores resultados), eficiente (en menos tiempo y con dosis más bajas), segura (con menos y más leves complicaciones), cómoda (menos molestias y autonomía) y accesible (para más personas, a menores costos). Con tecnología de ADN recombinante se dispone ahora de todas las gonadotrofinas e incluso algunas con formas moleculares modificadas para aumentar la duración de acción y disminuir el número de inyecciones. El esquema más utilizado es el de FSH recombinante junto con antagonistas de GnRH. Hay indicaciones específicas para agregar LH o coadyuvantes como hGH o andrógenos transdérmicos. La estimulación ovárica, además de infertilidad, se usa para la preservación de la fertilidad. Cada vez se implementan más estrategias como acumulación de óvulos, esquemas no convencionales (random start, DuoStim y otros) junto a vitrificación ovular, estudio genético preimplantatorio, transferencias embrionarias diferidas y la investigación continúa. Se pronostican mejoras en un futuro próximo, entre otras antagonistas por vía oral y estudio genético de pacientes para diagnosticar mutaciones o polimorfismos de gonadotrofinas y sus receptores. Aunque ya es factible individualizar la estimulación y volverla más efectiva, segura y amigable, así como ofrecer otras opciones a pacientes de mal pronóstico.

Due to an increased understanding of reproductive physiology and to the availability of more and better diagnostic/therapeutic agents, ovarian stimulation through individualization, has become more effective (improved results), efficient (shorter span and lower doses), safe (less and milder complications), comfortable (less discomfort and dependance) and affordable (for more people at lower cost). All gonadotrophins are now available by recombinant DNA technology, including some modified compounds for specific purposes such as longer action and fewer injections. The most popular ovarian regime uses recombinant FSH and GnRH antagonist. There are precise indications for adding LH or adjuncts like hGH or transdermal androgens. Besides infertility, ovarian stimulation is also indicated for fertility preservation. Strategies like oocyte accumulation, non-conventional stimulation protocols (random start, DuoStim and others), oocyte vitrification, preimplantation genetic testing, freeze-all, deferred embryo transfer for particular cases are becoming popular, and the research still goes on. Future advances like oral GnRH antagonists, and the study of mutations and polymorphisms for gonadotropins and its receptors are foreseen. Today through individualization, ovarian stimulation is safe, effective and friendly, also we can offer good options to bad prognosis patients

Hysteroscopic polypectomy versus expectant management in endometrial polyps in asymptomatic infertile women: a meta-analysis

Background: Endometrial polyp is a hyperplastic structural abnormality of the uterine cavity and is one of the most commonly found intrauterine abnormalities. The endometrial polyp is mostly asymptomatic and sometimes diagnosed only during infertility investigation. The influence of endometrial polyps on female infertility is not completely understood, however, due to the possibility of endometrial polyps influencing fertility, their removal is usually performed in women undergoing infertility treatment.Methods: This meta-analysis was performed through an electronic search using MEDLINE, PubMed in October 2017, bringing together the terms of interest in order to select studies that would compare polypectomy and expectant management for endometrial polyps in sub fertile women. Four articles were selected according to the inclusion and non-inclusion criteria.Results: Five variables were collected from the selected articles to be compiled and analyzed (rate of live births per transferred embryo, chemical pregnancy rate, spontaneous abortion rate, implantation rate and clinical pregnancy rate), none of which showed any difference statistically significant in conduct.Conclusions: The data concluded that there is no statistical significance between expectant management and polypectomy.

Evaluación de la tasa de blastocistos euploides en fase folicular y lútea (DuoStim) en mujeres con pobre respuesta ovárica: estudio preliminar en México / Euploid blastocyst rate in follicular vs luteal phase (DuoStim) in women with poor ovarian response: Preliminary study in Mexico

Resumen: OBJETIVO: Comparar la tasa de blastocistos euploides obtenida después de la estimulación ovárica en fase folicular con la fase lútea en un mismo ciclo menstrual en pacientes con deficiente respuesta ovárica. MATERIALES Y MÉTODOS: Estudio clínico, prospectivo y comparativo llevado a cabo en el Centro de Reproducción Arcos, Nascere, entre los meses de enero a julio de 2019. Se incluyeron pacientes con pobre respuesta ovárica según los criterios de Bologna y con indicación de PGT-A. Las estimulaciones en fase folicular y lútea se efectuaron con antagonista de la GnRH y FSHr/LHr (2:1) a partir del día 3 del ciclo y 5 días después de la primera recuperación de los ovocitos. Para completar el proceso de maduración ovocitaria se utilizaron análogos de GnRH, se tomó una biopsia de trofoectodermo en día 5-7. RESULTADOS: Se estudiaron 20 pacientes. Al comparar la fase folicular con la lútea la tasa de fertilización fue de 79% (IC95%: 29-46) vs 55% (IC95%: 34-53), la tasa de blastocistos 42% (IC95%: 19-44) vs 45% (IC95%: 24-55) y la tasa de blastocistos euploides 100% (IC95%: 44-53) vs 70% (IC95%: 38-46), respectivamente. Solo la tasa de recuperación de ovocitos en metafase II mostró diferencias significativas entre ambas fases 40% (IC95%: 18-37) vs 59% (IC95%: 31-59), p = 0.0333 en la fase folicular y lútea, respectivamente. CONCLUSIONES: La estimulación ovárica bifásica (folicular-lútea), en el mismo ciclo menstrual (DuoStim), resultó en mayor tasa de recuperación de ovocitos en metafase II durante la fase lútea. Sin embargo, las tasas de desarrollo embrionario a día 5-6 (blastocistos) y de embriones euploides fueron similares entre ambas fases.

Abstract: OBJECTIVE: Euploid blastocyst rate comparison between ovarian stimulation in follicular vs luteal phase performed in the same menstrual cycle in patients with poor ovarian response. MATERIALS AND METHODS: Clinical, prospective and comparative study conducted at Centro de Reproducción Arcos S.C., "Nascere", during january-july, 2019. Patients with PGT-A indication and poor ovarian response according to Bologna criteria were included. Under a short GnRH-antagonist protocol, stimulations, both in follicular and luteal phase were performed using rFSH/rLH (2:1) from day 3 of the cycle and 5 days after the first oocyte retrieval. In addition, ovulation trigger with an GnRH agonist was used, finally, on day 5-6 of embryo development, trophoctoctoderm biopsy was performed. RESULTS: In this study, 20 patients were included; when comparing follicular phase vs luteal phase, we found that fertilization rate was 79% (95%CI 29-46) vs 55% (95%CI 34-53), blastocysts rate was 42% (95%CI 19-44) vs 45% (95%CI 24-55) and euploid embryo rate was 100% (95%CI 44-53) vs 70% (95%CI 38-46). Only the oocyte recovery rate in metaphase II showed significant differences between both phases 40% (IC 95% 18-37) vs 59% (IC 95% 31-59), p=0.0333. CONCLUSION: Biphasic ovarian stimulation (follicular/ luteal) in the same menstrual cycle (DuoStim) resulted in a higher metaphase II ooctye recovery rate during the luteal phase in comparison with the follicular phase. However, the rates of blastocysts and euploid blastocysts were similar between both phases.

Hysteroscopic salpingosonography: a novel technique for infertile patients

Background: Infertility is akin to curse in our country. Patients of infertility run from pillar to post to get relief. Government Hospitals in India lie at the tail end of window-shopping of infertility centres by the patients having exhausted all their resources. Patients report without any detailed records, lost reports, coming after long hiatus of having stopped treatment in desperation, making one wonder how to proceed. At the other end are patients who have undergone laparotomy for various reasons like intestinal obstruction, tubercular abdomen, adnexal masses and their tubal status is not very clear on HSG. So, repeat laparoscopy in the former group and performing ab initio in the latter, involves putting the patients to the risk of general anesthesia, injury to internal organs due to anticipated adhesions. Although Hassan’s technique of open trocar entry is well accepted the first port entry, whatever be the mode, is an entry open to risks.Methods: In a selected group of infertile women, a baseline TVS was done on 2/3 day of menses and on the 7/8 day of menstrual cycle hysteroscopy was done which was immediately followed by another transvaginal ultrasound. The descriptive statistics is presented in the form of percentages and appropriate graphs.Results: Among the 54 patients who underwent this procedure, 65% had normal uterine cavity. 18% were referred for IVF. 9.2% conceived post procedure.Conclusions: Successive use of transvaginal ultrasound after hysteroscopy i.e Hysteroscopic sonosalpingography is a useful procedure in a select group of infertile patients.

Modified ovarian response prediction index: a novel index for ovarian response prediction in GnRH agonist cycles

Background: Evaluation of the ovarian reserve is necessary to achieve an appropriate controlled ovarian stimulation (COS). This can be done by correctly predicting the ovarian response. The objective of this study was to derive a simple index by combining the above parameters which will be helpful determining ovarian response.Methods: This retrospective analysis was performed at Guru hospital, Madurai, involving 162 patients between July 2016 and July 2018. Inclusion criteria was all patients attending for their first ICSI (intracytoplasmic sperm injection) cycle between the above period, GnRH agonist protocol as the method of ovarian stimulation, no history of any previous ovarian surgery, presence of both ovaries and no evidence of any obvious endocrine disorders. We calculated MORPI values by multiplying the AMH (ng/ml) level by the number of antral follicles (2-9 mm), and the result was divided by the age (years) of the patient and the day- 3 serum FSH level.Results: At a cut-off value of 35 (AUC-0.952) for collection of ≥ 4 oocytes and 140 (AUC-0.952) for collection of ≥ 15 oocytes, MORPI was found to have optimum sensitivity and specificity under ROC curve analysis.Conclusions: MORPI is a simple, precise and cost effective index to predict a low ovarian response, the collection of >4 MII oocytes and an excessive ovarian response in infertile women. This index also has a good ability to predict the clinical pregnancy rate. This might be used to improve the cost-benefit ratio of ovarian stimulation regimens.

Correlation between Ovarian Reserve and Incidence of Ectopic Pregnancy after In Vitro Fertilization and Embryo Transfer

PURPOSE: To elucidate the correlation between ovarian reserve and the incidence of ectopic pregnancy (EP) following in vitro fertilization and embryo transfer (IVF/ET) cycles. MATERIALS AND METHODS: In this observational study, 430 fresh IVF/ET cycles were examined from patient data of two university hospital infertility clinics. All included patients were positive for β-human chorionic gonadotropin (hCG) at 2 weeks after oocyte retrieval via controlled ovarian stimulation. For each cycle, information on age, duration of infertility, basal follicle stimulating hormone (FSH), anti-Müllerian hormone (AMH), days of ovarian stimulation, numbers of retrieved oocytes and transferred embryos, and pregnancy outcomes was collected. Patients with AMH lower than 1.0 ng/dL or basal FSH higher than 10 mIU/mL were classified into the decreased ovarian reserve (DOR) group, and the remaining patients were classified into the normal ovarian reserve (NOR) group. RESULTS: In total, 355 cycles showed NOR, and 75 cycles DOR. There were no significant differences between the DOR and NOR groups regarding intrauterine (74.7% vs. 83.4%, respectively) or chemical (14.7% vs. 14.1%, respectively) pregnancies. The DOR group had a higher EP than that of NOR group [10.7% (8/75) vs. 2.5% (9/355), p=0.004]. In both univariate [odds ratio (OR) 5.6, 95% confidence interval (CI) 1.4–9.6, p=0.011] and multivariate (adjusted OR 5.1, 95 % CI 1.1–18.7, p=0.012) analysis, DOR was associated with a higher risk of EP. CONCLUSION: DOR may be associated with a higher risk of EP in IVF/ET cycles with controlled ovarian stimulation. More careful monitoring may be necessary for pregnant women with DOR.

Ovarian Stimulation and In Vitro Maturation for Fertility Preservation in Female Cancer Patients / 中山大学学报(医学科学版)

@#【Objective】To determine the effect of ovarian stimulation or in vitro maturation for fertility preservation in female cancer patients. 【Methods】 A retrospective study was conducted in 27 females who underwent fertility preservation procedures in our center.【Results】Female patients were included in this study with an average age of 27.1. Patients spent on average for 6.8 d to retrieve oocytes since their attendance day. Total amount of Gn was on average 910 U per patient and for patients with breast cancer，the average estrogen level on trigger day reached 360 pg/mL. The maturation rate of oocytes from ovarian stimulation cycles was 82.6% ，which of that in emergency in- vitro maturation cycles was 38.1%.【Conclusion】The development capability of oocytes from cancer patients are comparable with those of other infertility patients. Peak estradiol levels were controlled by the administration of letrozole. In vitro maturation of oocytes performed at random time of the menstrual cycle may result in a lower maturation rate ，which is associated with the time limit of the follow- up cancer treatment. In conclusion，clinicians should consider a more holistic approach for female cancer patients，which focuses not only on the characteristic of the primary cancer but also on the phase of the menstrual cycle at their attendance day.

¿Cuál es el punto de corte más significativo de hormona antimülleriana como predictor de la respuesta ovárica, tasa de embarazo y nacido vivo? / What is the most significant cutting point of antimüllerian hormone as a predictor of the ovarian response, pregnancy rate and living born?

Resumen OBJETIVO: Evaluar la eficacia de la hormona antimülleriana en la predicción de la respuesta ovárica, tasa de embarazo y nacido vivo. MATERIALES Y MÉTODOS: Estudio retrospectivo, analítico y observacional efectuado para evaluar los ciclos de estimulación ovárica de pacientes atendidas entre el 1 de enero de 2010 y el 30 de junio de 2017 en el Centro de Reproducción Hisparep. Criterios de inclusión: límites de edad 20 y 44 años y tener ciclos menstruales regulares. Criterios de exclusión: factor masculino alterado, cavidad uterina alterada, trastornos endocrinos, antecedente de daño ovárico. Variables de estudio: concentraciones de hormona antimülleriana, ovocitos recuperados, maduros, fecundados, embriones, tasa de embarazo y nacido vivo. Las variables cuantitativas se analizaron mediante una comparación de medias con t de Student, las variables porcentuales mediante comparación de percentiles. RESULTADOS: Se evaluaron 223 ciclos, divididos en grupos según diferentes puntos de corte. En cualquier punto de corte la hormona antimülleriana predice mayor recuperación de ovocitos maduros y fecundados: 1.25 ng/mL fue el punto de corte más significativo porque predijo mayor obtención de embriones. Se observó relación entre las tasas de embarazo clínico y nacido vivo, aunque su poder predictivo fue débil. Tomar como referencia un punto de corte de 0.5 ng/mL parece predecir bajas probabilidades de nacido vivo. CONCLUSIONES: La hormona antimülleriana fue el mejor marcador de respuesta ovárica; el punto de corte más significativo fue el de 1.25 ng/mL. Hacen falta más estudios para evaluar su eficacia como predictor de bajas tasas de nacido vivo.

Abstract OBJECTIVE: To evaluate the efficacy of antimülleriana hormone in prediction of the ovarian response, pregnancy rate and live birth. MATERIALS AND METHODS: In this retrospective, analytical and observational study, ovarian stimulation cycles were evaluated at the Hisparep Reproduction Center, in a period from January 1, 2010 to June 30, 2017, the inclusion criteria were; Age from 20 to 44 years and regular menstrual cycles. The exclusion criteria; altered male factor, altered uterine cavity, endocrine disorders, antecedent of ovarian damage. The study variables; antimüllerian hormone, oocytes recovered, mature, fertilized, embryos, pregnancy rate and live birth. The quantitative variables were analyzed by means of a comparison of means, using the Student's T test, the percentage variables by means of comparison of percentiles. RESULTS: 223 cycles were evaluated, divided into groups using different cut points. It was determined that Antimullerian Hormone predicts a greater recovery of mature and fertilized oocytes using any cut point, we consider that 1.25 ng / mL was the most significant cutoff point, since it predicts higher embryo obtaining, relationship was observed in pregnancy rates clinical and live birth, although its predictive power is weak, however, using a cutoff of 0.5 ng / mL seems to predict low odds of live birth CONCLUSIONS: Antimullerian hormone is the best marker of ovarian response, we consider that 1.25 ng /mL is the most significant cut-off point, more studies are needed to evaluate its efficacy as a predictor of low rates of live birth.

Electrophysiological responses to different follicle-stimulating hormone isoforms on human cumulus oophorus cells: preliminary results / Respostas eletrofisiológicas a diferentes isoformas de FSH em células humanas do cumulus oophorus: resultados preliminares

Abstract Objective The aim of the present study was to provide a better understanding of the specific action of two follicle-stimulating hormone (FSH) isoforms (β-follitropin and sheep FSH) on the membrane potential of human cumulus cells. Methods Electrophysiological data were associated with the characteristics of the patient, such as age and cause of infertility. The membrane potential of cumulus cells was recorded with borosilicate microelectrodes filled with KCl (3 M) with tip resistance of 15 to 25 MΩ. Sheep FSH and β-follitropin were topically administered onto the cells after stabilization of the resting potential for at least 5 minutes. Results In cumulus cells, the mean resting membrane potential was - 34.02 ± 2.04 mV (n = 14). The mean membrane resistance was 16.5 ± 1.8 MΩ (n = 14). Sheep FSH (4 mUI/mL) and β-follitropin (4 mUI/mL) produced depolarization in the membrane potential 180 and 120 seconds after the administration of the hormone, respectively. Conclusion Both FSH isoforms induced similar depolarization patterns, but β-follitropin presented a faster response. A better understanding of the differences of the effects of FSH isoforms on cell membrane potential shall contribute to improve the use of gonadotrophins in fertility treatments.

Resumo Objetivo O objetivo do presente estudo foi fornecer uma melhor compreensão da ação específica de duas isoformas de hormônio folículo estimulante (FSH, sigla em inglês) (β-folitropina e FSH ovino) no potencial de membrana de células do cumulus oophorus humanas. Métodos Dados eletrofisiológicos foram associados às características da paciente, como idade e causa da infertilidade. O potencial de membrana das células do cumulus foi registrado com microeletrodos de borossilicato preenchidos com KCl (3 M) com uma resistência de 15 a 25 MΩ. O FSH ovino e a β-folitropina foram administrados topicamente nas células após a estabilização do potencial de repouso durante pelo menos 5 minutos. Resultados Nas células do cumulus, o potencial médio de membrana em repouso foi de -34,02 ± 2,04 mV (n = 14). A resistência média da membrana foi de 16,5 ± 1,8 MΩ (n = 14). O FSH ovino (4 mUI/mL) e a β-folitropina (4 mUI/mL) produziram despolarização no potencial de membrana 180 e 120 segundos após a aplicação do hormônio, respectivamente. Conclusão Ambas as isoformas de FSH induzem padrões de despolarização semelhantes, mas a β-folitropina apresentou uma resposta mais rápida. Uma melhor compreensão das diferenças dos efeitos das isoformas do FSH no potencial da membrana celular contribuirá para aprimorar o uso das gonadotrofinas no estímulo ovariano controlado e em protocolos de maturação oocitária in vitro.

Effect of Progestin-primed Ovarian Stimulation Protocol on Outcomes of Aged Infertile Women Who Failed to Get Pregnant in the First IVF/ICSI Cycle: A Self-controlled Study / 华中科技大学学报（医学）（英德文版）

This study aimed to explore the outcomes of progestin-primed ovarian stimulation protocol (PPOS) in aged infertile women who failed to get pregnant in the first IVF/ICSI-ET cycles with GnRH-a long protocol.A self-controlled study was conducted to retrospectively investigate the clinical outcomes of 104 aged infertile patients who didn't get pregnant in the first IVF/ICSI-ET treatment by stimulating with GnRH-a long protocol (non-PPOS group),and underwent PPOS protocol (PPOS group) in the second cycle between January 2016 and December 2016 in the Center for Reproductive Medicine,Renmin Hospital of Wuhan University.The primary outcomes included clinical pregnancy rate of frozen-thawed embryos transfer (FET) in PPOS group,and good-quality embryo rate in both groups.The secondary outcomes were fertilization rate,egg utilization rate and cycle cancellation rate.The results showed that there were no significant differences in basal follicle stimulating hormone (bFSH),antral follicle count (AFC),duration and total dosage of gonadotropin (Gn),number of oocytes retrieved,intracytoplasmic sperm injection (ICSI) rate,fertilization rate,and cycle cancellation rate between the two groups (P＞0.05).However,the oocyte utilization rate and good-quality embryo rate in PPOS group were significantly higher than those in non-PPOS group (P＜0.05).By the end of April 2017,62 FET cycles were conducted in PPOS group.The clinical pregnancy rate and embryo implantation rate were 22.58％ and 12.70％,respectively.In conclusion,PPOS protocol may provide better clinical outcomes by improving the oocyte utilization rate and good-quality embryo rate for aged infertile patients who failed to get pregnant in the first IVF/ICSI-ET cycles.

Effect of Progestin-primed Ovarian Stimulation Protocol on Outcomes of Aged Infertile Women Who Failed to Get Pregnant in the First IVF/ICSI Cycle: A Self-controlled Study / 华中科技大学学报（医学）（英德文版）

This study aimed to explore the outcomes of progestin-primed ovarian stimulation protocol (PPOS) in aged infertile women who failed to get pregnant in the first IVF/ICSI-ET cycles with GnRH-a long protocol.A self-controlled study was conducted to retrospectively investigate the clinical outcomes of 104 aged infertile patients who didn't get pregnant in the first IVF/ICSI-ET treatment by stimulating with GnRH-a long protocol (non-PPOS group),and underwent PPOS protocol (PPOS group) in the second cycle between January 2016 and December 2016 in the Center for Reproductive Medicine,Renmin Hospital of Wuhan University.The primary outcomes included clinical pregnancy rate of frozen-thawed embryos transfer (FET) in PPOS group,and good-quality embryo rate in both groups.The secondary outcomes were fertilization rate,egg utilization rate and cycle cancellation rate.The results showed that there were no significant differences in basal follicle stimulating hormone (bFSH),antral follicle count (AFC),duration and total dosage of gonadotropin (Gn),number of oocytes retrieved,intracytoplasmic sperm injection (ICSI) rate,fertilization rate,and cycle cancellation rate between the two groups (P＞0.05).However,the oocyte utilization rate and good-quality embryo rate in PPOS group were significantly higher than those in non-PPOS group (P＜0.05).By the end of April 2017,62 FET cycles were conducted in PPOS group.The clinical pregnancy rate and embryo implantation rate were 22.58％ and 12.70％,respectively.In conclusion,PPOS protocol may provide better clinical outcomes by improving the oocyte utilization rate and good-quality embryo rate for aged infertile patients who failed to get pregnant in the first IVF/ICSI-ET cycles.

Comparsion of GV oocytes transcriptome between PCOS patients and normal ovulatory women / 吉林大学学报(医学版)

Objective: To investigate the effects of controlled ovarian stimulation (COS) on the differentially expressed genes in GV oocytes and main signal transduction pathways in the polycystic ovary syndrome (PCOS) patients and the normal ovulatory women, and to screen the key genes impacting the development of oocytes of the PCOS patients. Methods: During controll ovarian hyperstimulation with GnRH-a long protocol, 3 patients with PCOS (PCOS group) and 3 normal ovulatory women due to male infertility factor (control group) were selected. Enzyme digestion was used to islolate the granule cells. The dumped immature oocytes were collected after intracytoplasmic sperm injection (ICSI). The cDNA library was constructed and sequencing was performed in Illumina MiSeq sequencing platform and RT-PCR was used to confirm the data obtained in vivo. Results: A total of 510 024 82 sequence reads were obtained, and 8 G base sequence information were contained. A total of 63 differentially expressed genes were found by bio-informatics software, including 19 significant up-regulation genes and 44 significant down-regulation genes (Fold Change>4, FDR<0. 01). The expression levels of vascular endothelial growth (VEGF) and fatly acid dehydrogenase 1 (FADS1) mRNA in the patients in PCOS group were significantly higher than those in control groups (P

Tasa acumulada de embarazo clínico y en curso en ciclos de inseminación intrauterina y análisis de los ciclos según la edad, conteo de folículos maduros y estimulación con antagonista de GnRH / Clinical and ongoing cumulative pregnancy rates in cycles of intrauterine insemination and analysis of the cycles according to age, follicular count and GnRH antagonist use

Resumen Objetivo: Determinar la tasa acumulada de embarazo clínico en ciclos de inseminación intrauterina en pacientes estimuladas con gonadotropinas según el número de folículos maduros desarrollados y edad, así como la influencia de los antagonistas de GnRH en su desarrollo y en la tasa de embarazo. Materiales y métodos: Estudio analítico, retrospectivo, en el que se evaluaron ciclos de inseminación intrauterina de pacientes con diferentes protocolos de gonadotropinas en un periodo de dos años. La muestra se dividió en grupos: menores de 35 y más o menos mayores de 35 años y uso o no de antagonista de GnRH. Resultados: Se evaluaron 229 ciclos de inseminación intrauterina en 172 pacientes; de éstas 64% eran menores de 34 años (grupo 1) y 36% mayores de 35 años. El 50% de las pacientes desarrolló de 2 a 3 folículos maduros y 10% de 4 a 6, con una tendencia en aumento de la tasa de embarazo con el desarrollo de hasta 4 folí culos maduros. El antagonista de GnRH no parece relacionarse con mejores tasas de embarazo clínico o en curso en ciclos con más de un folículo maduro. La tasa acumulada de embarazo clínico en tres ciclos fue de 40.6%, mientras que la tasa acumulada de embarazo en curso fue 26.1%. Conclusiones: Hubo relación proporcional entre el número de folículos maduros desarrollados y la tasa de embarazo clínico y en curso. La edad no parece haber tenido influencia en las tasas de em barazo y no pudo demostrarse la eficacia del antagonista en ciclos con desarrollo multifolicular.

Abstract Objective: To determine the cumulative clinical pregnancy rate in cycles of intrauterine insemination with gonadotropin stimulation in relation to number of mature follicles and age and the use of GnRH antagonist on its development. Materials and methods: Analytical, retrospective study in which intrauterine insemination cycles of patients with different gonadotropin protocols were evaluated over a period of two years. The patients were divided in two groups: <35 and ≥35 years old and the use of GnRH antagonist. Results: We evaluated 229 cycles of intrauterine insemination in 172 patients; Of these 64% were under 34 years old (group 1) and 36% over 35 years. The use of antGnRH did not appear to have relation with better clinical and ongoing pregnancy rates in cycles with more than one mature follicle. The cumulative pregnancy rate in three cycles was 40.6%, and cumulative ongoing pregnancy rates was 26.1%. Conclusions: The more mature follicle developed the higher clinical and ongoing pregnancy rates. The age did not appear to have influence in the pregnancy rates, there is no better pregnancy rates with use of antGnRH in cycles with multifolicular developed.

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.

Protocolos de estimulación ovárica en inseminación artificial según el patrón utilizado de glicosilación de la hormona folículo estimulante / The impact of different ovarian stimulating protocols in artificial insemination based on the glycosylation pattern of the follicle stimulating hormone

Resumen ANTECEDENTES: los estudios clínicos que comparan diferentes protocolos de estimulación ovárica no son concluyentes. Nuestro estudio compara tres protocolos según el patrón de glicosilación de la hormona folículo estimulante (FHS) que imita el ciclo natural para inseminación artificial. OBJETIVO: proponer un protocolo de estimulación ovárica secuencial con FSH urinaria (isoforma ácida) seguido de FSH recombinante (isoforma menos ácida) y evaluar su efectividad respecto de los esquemas tradicionales de estimulación con FSH recombinante (FSHr) y FSH urinaria (FSHu). MATERIALES Y MÉTODOS: estudio de cohortes, retrospectivo, efectuado entre mayo de 2012 y mayo 2015 en parejas infértiles en protocolo de inseminación artificial. El grupo de estudio se dividió en tres: 1) FSHr, 2) FSHhp y 3) estimulación sequencial: FSHhp + FSHr. Para el análisis estadístico se utilizaron χ2, ANOVA o test Mann-Whitney. Los resultados se reportan con límite de significación de p < 0.05. RESULTADOS: se estudiaron 178 parejas infértiles en protocolo de inseminación artificial y se efectuaron 299 ciclos de estimulación ovárica con inseminación artificial; grupo 1) 99 con FSHr, 2)100 con FSHhp y 3) 100 con estimulación sequencial: FSHhp + FSHr. Los resultados gestacionales fueron mayores en el grupo FSHu y secuencial. En el análisis costo-efectividad se observó menor tasa con el esquema secuencial en comparación con los otros dos. Al comparar los tres protocolos según los intentos previos de inseminación, en la serie con intentos previos, se encontraron diferencias estadísticamente significativas en βHCG y gestación al comparar FSHr versus secuencial. El protocolo FSHr fue menos efectivo que los otros dos tratamientos. CONCLUSIONES: se planteó la estimulación ovárica controlada con protocolo secuencial en pacientes que recibirían inseminación artificial y, aunque no se encontraron diferencias significativas, sí se observó una tendencia en la que tanto la dosis como los días de estimulación requerida son menores con este protocolo que con los clásicos con FSHr o FSHu.

Abstract BACKGROUND: Earlier trials comparing different ovarian stimulating protocols in assisted reproduction found no significant differences in the results. OBJECTIVE: To evaluate the effect of three different stimulation protocols based on the glycosylation pattern of the follicle stimulating hormone (FSH) in an intrauterine insemination (IUI) program. The stimulating protocols are: human FSH (acidic isoform), recombinant FSH (less acidic isoform) and combined urinary and recombinant FSH. MATERIALS AND METHODS: Cohort study, retrospective, conducted between May 2012 and May 2015 in infertile couples in protocol of artificial insemination. The study group was divided into three: 1) FSHr, 2) FSHhp and 3) sequential pacing: FSHhp + FSHr. For statistical analysis, χ2, ANOVA or Mann-Whitney test were used. The results are reported with a significance limit of p < 0.05. RESULTS: 178 infertile couples were studied in an artificial insemination protocol and 299 cycles of ovarian stimulation were performed with artificial insemination; Group 1) 99 with FSHr, 2) 100 with FSHhp and 3) 100 with sequential stimulation: FSHhp + FSHr. CONCLUSION: In this study, controlled ovarian stimulation with sequential protocol was considered in patients who would receive artificial insemination and, although no significant differences were found, a trend was observed in which both the dose and the days of stimulation required are lower with this protocol than with the classics with FSHr or FSHu.

Indução de ovulação em pacientes com tumor estrogênio­dependente: diretrizes clínicas da Sociedade Brasileira de Reprodução Humana / Ovulation induction in patients with estrogen­dependent tumors: a Brazilian Society of Human Reproduction clinical practice guideline

A oncofertilidade é um campo de interesse interdisciplinar de desenvolvimento recente que busca mesclar os conhecimentos em oncologia e medicina reprodutiva, com a contribuição das técnicas de reprodução assistida, para o desenvolvimento de estratégias de preservação da função gonadal e oferecer a possibilidade da procriação biológica aos sobreviventes de câncer. As estratégias de preservação da fertilidade feminina em pacientes oncológicas atualmente aceitas para a prática rotineira são a criopreservação de embriões e a criopreservação de oócitos maduros. Ocorre que, para execução de ambos, a indução de ovulação é obrigatória e, com ela, vêm os riscos teóricos de estimulação do crescimento de tumores estrogênio­dependentes e a postergação do início do tratamento antineoplásico. Os protocolos de estimulação ovariana de início aleatório contemplam a intenção de se minimizar o atraso no início da quimioterapia ou radioterapia e o bloqueio ao crescimento tumoral e oferecem resultados satisfatórios, semelhantes aos obtidos em protocolos de início habitual. Apresentamos neste artigo as diretrizes clínicas da Sociedade Brasileira de Reprodução Humana para indução de ovulação em pacientes com tumor estrogênio­dependente.(AU)

Oncofertility is an interdisciplinary interest field of recent development, which aims to merge the knowledge in oncology and reproductive medicine, with the help of assisted reproductive technologies, to develop strategies for gonadal function preservation and to offer the possibility of biological procreation to cancer survivors. Preservation strategies of female fertility in oncological patients currently accepted for routine practice are the cryopreservation of embryos and cryopreservation of mature oocytes. It happens that ovulation induction is mandatory for executing both strategies, and with it the theoretical risk of stimulation of estrogen­dependent tumors growth and the postponement of anti­neoplastic treatment. Random­start ovarian stimulation protocols include the intention of minimizing the delay in onset of chemo­radiotherapy and to block tumor growth, providing satisfactory results, similar to those obtained in the usual beginning protocols. This article presents the clinical guidelines of the Brazilian Society of Human Reproduction for ovulation induction in patients with estrogen­dependent tumors.(AU)

Effectiveness of Gonadotropin-Releasing Hormone Antagonists in the Management of Multifollicular Recruitment in Intrauterine Insemination Cycles.

Introduction: To evaluate the efficacy of GnRH antagonists in terms of increasing the pregnancy rates in intrauterine insemination (IUI) after controlled ovarian stimulation (COS) when more than one dominant follicle is recruited. Methods: This is a prospective and randomized clinical trial that included 300 couples with primary or secondary infertility that underwent their first or second COS-IUI cycle with recombinant FSH. In all of these patients two or three leading follicles > 14 mm of mean diameter where detected by vaginal ultrasound (US) and were randomized into two groups. In group A the patients received rFSH+GnRH antagonists until the day that the hCG was given, while in group B the patients followed a standard COS received rFSH only. Results: Total amount of rFSH units (620.8+245.1vs 575.5+296.4) and clinical pregnancy rates (31.16% vs 19.15%) were statistically significantly higher in patients who were treated with GnRH antagonists. A similar number of twin pregnancies and miscarriages occurred in both groups. Conclusion: Multiple doses of GnRH antagonists in COS-IUI significantly increase pregnancy rates in multifollicular cycles.