Estimulación Ovárica Controlada para Inseminación Intrauterina, una revisión / Controlled ovarian stimulation for intrauterine insemination, a review

La inseminación intrauterina es una de las técnicas más utilizadas en el manejo de la infertilidad. Sus indicaciones van desde ciclos anovulatorios o factor masculino leve, hasta parejas del mismo sexo o mujer soltera. Desde sus inicios, se han descrito diversos protocolos de estimulación ovárica. Probablemente el más utilizado sea el uso de clomifeno vía oral, debido a lo sencillo, económico y disponibilidad del mismo. No obstante, las nuevas tecnologías y el uso de gonadotropinas urinarias o recombinantes, han permitido mejorar los resultados en aquellos casos donde se observa una resistencia al clomifeno. La decisión sobre cuál es el mejor protocolo para una estimulación ovárica en inseminación intrauterina, no se basa simplemente en buscar el mejor fármaco, se deben considerar factores como el diagnóstico, la presencia o no de ciclos ovulatorios, el coste y disponibilidad de los medicamentos, entre otros. Es el propósito de este trabajo, realizar una revisión de las indicaciones y resultados para poder establecer y/o sugerir pautas de manejo

Intrauterine insemination is one of the most popular techniques for the management of infertility. Among its indications are anovulation, mild male factor, same sex couple and single woman. There are several controlled ovarian stimulation protocols that are being described. Probably, the most common drug is clomiphene citrate because of its simplicity, cost and availability. Nonetheless, the introduction of gonadotropins, either urinary or recombinant, has shown to be an efficient alternative especially in those cases of clomiphene resistance. The decision about which protocol has the best results is not based only on the drug used. We need to consider other factors like infertility factor, presence of ovulatory or anovulatory cycles, cost and availability of drugs. It is the purpose of the present paper, to review the indications and most recent evidence in order to establish or suggest guidelines for treatment

Vaginosis bacteriana y candidiasis vaginal: análisis de una nueva alternativa terapéutica / Bacterial vaginosis and vaginal candidiasis: analysis of a new therapeutic alternative

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Embarazo múltiple posterior a la transferencia de embrión único: serie de casos y revisión de la literatura / Multiple pregnancies after single embryo transfer: case report and literature review

El embarazo gemelar es la complicación más frecuente tras técnicas de reproducción asistida (TRA). En un esfuerzo por disminuir su incidencia, cada vez más centros adoptan la medida de transferencia de embrión único. Sin embargo, a pesar de estas medidas, se ha observado que existe un riesgo elevado de duplicación embrionaria inherente a las TRA cuyo mecanismo permanece desconocido. En el presente trabajo presentamos una serie de casos y una revisión de la literatura acerca de los posibles mecanismos y teorías involucradas en dichos acontecimientos (AU)

Twin pregnancy is the most frequent complication for the assisted reproduction techniques. A strategy for reducing its incidence, many IVF centres have adopted a policy of single embryo transfer. However, despite these efforts, a risk of multiple pregnancies is still present and the mechanisms for its occurrence are unknown. We present a number of cases and a literature review discussing the theories and possible mechanisms involved (AU)

Comparación de resultados perinatales entre gestaciones gemelares espontáneas y las provenientes de técnicas de reproducción asistida / Comparison between spontaneous twin pregnancy and ivf twin pregnancy perinatal outcomes

OBJETIVO: Evaluar si las técnicas de reproducción asistida influyen sobre los resultados perinatales del embarazo gemelar. Sujetos y métodos: Estudio de revisión de resultados perinatales en embarazos gemelares en una clínica privada en el que se incluyen todos los embarazos gemelares espontáneos y por técnicas de reproducción asistida (TRA) que acuden a su atención obstétrica excluyendo aquellas mujeres con enfermedades preexistentes que supongan un resultado perinatal adverso. Se analizan 95 casos. RESULTADOS: No hubo diferencia estadística en términos de diabetes gestacional, presencia de preeclampsia, práctica de cesárea, peso promedio del recién nacido e ingreso a unidad de cuidados intensivos neonatales. Hubo diferencia estadística en los casos de anemia gestacional (61,29 % del grupo de gemelar espontáneo versus un 31,25 % del gemelar por TRA, p= 0,0075) y en el grupo de semanas de edad gestacional al momento del parto: 32-36,6 semanas (32,25 % para gemelar espontáneo y 65,62 % para gemelar por TRA, p = 0,0039) y en el de >37 semanas de gestación (58,08 % para gemelar espontáneo y 26,57 % para gemelar por TRA, p = 0,0059). CONCLUSIONES: Las técnicas de reproducción asistida se asocian con una mayor prevalencia de parto pretérmino

OBJECTIVE: To evaluate if assisted reproductive techniques affect perinatal outcomes of twin pregnancies. Subject and method: This is a review of perinatal outcomes of twin pregnancies in a private institution. All twin pregnancies detected were included and classified in two groups: spontaneous pregnancy and assisted reproduction (AR) pregnancy. Those women who had a preexistent condition that could represent an adverse outcome were excluded. 95 cases were included. RESULTS: There was no statistical difference in terms of gestational diabetes, preeclampsia, c-section, newborn weight and in those who required neonatal intensive care. There was statistical difference in gestational anemia (61.29 % vs 31.25 % for spontaneous twin pregnancy and assisted reproduction twin pregnancy respectively, p = 0.0075) and in two groups according to gestational weeks at delivery: 32-36.6 weeks (32.25 % for spontaneous twin pregnancy and 65.62 % for AR twin pregnancy, p = 0.0039) and >37 weeks at delivery (58.08 % for spontaneous twin pregnancy and 26.57 % for AR twin pregnancy, p = 0.0059). CONCLUSION: Assisted reproductive techniques associate with a higher prevalence of preterm labor

Reproducción Asistida: ¿Debemos solo transferir un embrión? / Assisted Reproduction: Should be transferred only one embryo?

OBJETIVO: Comparar resultados obstétricos y perinatales de embarazos únicos espontáneos con los obtenidos por reproducción asistida, tanto únicos como gemelares. MATERIAL Y MÉTODO: Estudio descriptivo observacional retrospectivo. Se analizan un total de 1 096 embarazos de pacientes que acuden a control obstétrico en una clínica privada y se clasifican en tres grupos según el modo de concepción y número de fetos: Grupo 1, embarazo único espontáneo; Grupo 2, embarazo único por técnica de reproducción asistida (TRA) y, Grupo 3, embarazo gemelar por reproducción asistida. Se analizan los resultados obstétricos y perinatales entre los tres grupos. Se considera que hay diferencia estadística con un valor menor a <0.01 utilizando la prueba de chi cuadrado. RESULTADOS: La tasa de diabetes gestacional fue mayor en el grupo de embarazo único por TRA (23,78%) comparada a la de embarazo único espontáneo (6,66%) y gemelar por TRA (0%), presentando diferencia estadísticamente significativa. Hubo mayor presencia de anemia gestacional en el grupo de embarazo único espontáneo (76,66%) que en los grupos de TRA (19,51% y 31,25% para único y gemelar respectivamente) con diferencia estadística. Se presenta diferencia significativamente estadística a favor del grupo de embarazo gemelar por TRA en cuanto a un mayor número de casos de amenaza de parto pretérmino (25 %), una mayor ganancia de peso materno a final del embarazo (12,33 ± 3,2 Kg), un mayor número de nacimientos por cesárea (81,25%), menor edad en semanas de gestación al parto (35,28 ± 3,6), menor peso del recién nacido (2 388,69 ± 378 g) y un mayor número de casos que requieren ingreso a unidad de cuidados intensivos neonatales (18,75%). CONCLUSIONES: El embarazo gemelar tiene un peor pronóstico perinatal que el embarazo único sea espontáneo o por TRA

OBJETIVE: To determine the correlation between the semen parameters (concentration, motility, morphology and vitality) and sperm DNA integrity, using the test Halosperm. Material And METHODS: Prospective study conducted at the Laboratory of Andrology of Assisted Reproduction Laboratory FERTILAB, Lima - Peru, from August 2012 to March 2013. 282 patients were analyzed. We have established the DNA fragmentation index (IFA) from patients with semen sample normozoospermic and patients with semen sample altered in some parameters. We used two types of threshold (18% and 30%) and were correlated with semen parameters. In the total population was determined the Spearman correlation between sperm parameters and the IFA. RESULTS: It was determined that the value of the median the IFA of the patients with semen sample normozoospermic was significantly lower than that patients with semen sample altered in some parameters (12.8% vs 19.0, P=0.000). Using threshold of 18% was determined the there significant difference between the median of the two groups (Group 1: ≤ 18% y Group 2: > 18%) in age (37 years vs 40 years, P = .002), sperm concentration (82.30 X 106/ml vs 58.00 X 106/ml, P = 0.046), progressive motility (45.80% vs 27.40, P = 0.000), normal morphology (12.50% vs 9.00%, P = 0.000) and sperm vitality (89.0% vs 78.0%, P = 0.000). Using the threshold of 30 % was found significant difference between the median of the two groups (Group 1: ≤ 30% y Group 2:> 30%) in age (39 years vs 44 years, P=0.000), sperm concentration ( 78.00 X 106/ml vs. 36.75  X 106/ml, P = 0.015 ), motility progressive (40.85% vs 22.38 %, P=0.000 ), normal morphology (12.0 % vs 6.0 %, P=0.004) and sperm vitality (85.0 % vs 72.5%, P=0.000). Also identified an inverse correlation between the IFA and concentration (r=- 0.219 P=0.000), progressive motility (r=-0.452 P=0.000), normal morphology (r=-0.322 P=0.000) and vitality (r = -0.452 P = 0.000) in the total population. We determined a significant positive correlation between age and the IFA (r=0.267 P = 0.000). CONCLUSIONS: The results indicate that the level of DNA damage in sperm patients with semen sample altered in some parameters is significantly higher than in patients with semen sample normozoospermic. It has been shown that the semen parameters (concentration, motility, morphology and vitality) are highly negatively correlated with sperm DNA fragmentation index. It showed a positive correlation between age and the IFA

Síndrome de Ovario Poliquístico: Donde estamos y hacia donde dirigirnos / Polycystic Ovary Syndrome: Where we are and where to go

OBJETIVO: Sintetizar la información con mayor relevancia sobre los criterios diagnósticos del SOP y revisar los principales estudios de prevalencia. Material Y método: Estudio de revisión de la literatura. Se realiza una búsqueda avanzada en MEDLINE con las siguientes palabras clave: PCOS AND diagnostico criteria, PCOS AND prevalence. RESULTADOS: Se obtienen más de 3000 artículos seleccionando 27 de ellos en base a su relevancia, autores, factor impacto de la revista y fecha de publicación. CONCLUSIONES: El SOP puede clasificarse en 4 fenotipos según la presencia de tres criterios diagnósticos: SOP clásico (oligo/anovulación + hiperandrogenismo + ovarios poliquísticos (OP)), SOP clásico sin OP (oligo/anovulación + hiperandrogenismo), SOP ovulatorio hiperandrogenismo + OP), SOP sin hiperandrogenismo (oligo/anovulación + OP). Consideramos que lo más importante y determinante será el establecer La morbilidad (problemas reproductivos, síndrome metabólico, enfermedad cardiovascular, riesgo de cáncer) para cada fenotipo o presentación del síndrome

OBJECTIVE: To analyze and discuss the latest in the literature about PCOS diagnostic criteria and to review today prevalence. MATERIAL AND METHOD: Review of the literature. A search in MEDLINE was performed with the following keywords: PCOS AND diagnostic criteria, PCOS and prevalence. RESULTS: There was over 3000 articles as a result and we selected 27 based on the relevance, authors, journal impact factor and date of publication. CONCLUSIONS: PCOS can be classified into four phenotypes according to the presence or not of three diagnostic criteria: Classic PCOS: (oligo/anovulation + hyperandrogenism + polycystic ovaries (PO)), Classic PCOS w/out PO (oligo/anovulation + hyperandrogenism), Ovulatory PCOS (hyperandrogenism + PO), PCOS w/out hyperandrogenism (oligo/anovulation + PO). We think that the most important step will be to establish each phenotype morbidity (in terms of reproductive problems, metabolic syndrome, ardiovascular disease risk, cancer risk)

[Polycystic ovary syndrome: is there a rise in the prevalence?]. / Síndrome de ovario poliquístico: Ha aumentado su prevalencia?

OBJECTIVE: To determine the prevalence of polycystic ovary syndrome (PCOS) according to the three major diagnostic criteria previously described in an unselected group of women from Spain and to identify the most common phenotypes of the disease. MATERIAL AND METHOD: An observational, transversal prevalence study was carried out between July 1 2014 and October 31 2014. All participants received a questionnaire and underwent a physical and trans-vaginal ultrasound examination. Blood samples were also collected for analysis of metabolic markers and hormones. PCOS was diagnosed according to three major criteria: NIH, Rotterdam and AE-PCOS criteria. Following diagnosis women with PCOS were assigned to one of four phenotypes. RESULTS: A total of 242 women were involved in the study. The prevalence for each major criteria was as follows: National Institute of Health (NIH) criteria had a prevalence of 1 4.88%, Rotterdam criteria had a prevalence of 29.34% and Androgen Excess and PCOS Society criteria presented a prevalence of 17.36%. The prevalence for each phenotype was: A, 40.85%; B, 25.35%; C, 8.45%; and D, 25.35%. PCOS women had more prevalence of hirsutism (36.61 %), infertility (25.35%), obesity (21.1 2%) and metabolic syndrome (11 .26%) than controls (7.01%, 6.43%, 5.84% and 2.33% respectively). CONCLUSION: There is a rise in the prevalence of PCOS in Caucasian population with the classic phenotype (oligo-anovulation, hyperandrogenism, polycystic ovaries) being the most common presentation of the syndrome.

[Proteomics and PCOS: Is it here the missing link? Literature review]. / Proteómica y síndrome de ovario poliquístico: ¿encontraremos aquí el eslabón perdido? Revisión de la bibliografía.

Polycystic ovary syndrome (PCOS) is known as a common gynecologic and endocrinology disease with multiple short and long-term consequences. It is one of the most common causes for hyperandrogenism and anovulation, increases the risk for metabolic syndrome, type 2 diabetes and cardiovascular disease. Its etiology remains unclear. PCOS is thought to be the result of the interaction between predisposing genetic variants with environmental factors and strongly depends on ethnicity. Proteomics allows the study of several hundreds or thousands of proteins in order to reveal physiological state of a tissue or an organ at the molecular level and to identify disease-specific biomarkers. Its use on PCOS patients will permit us to identify molecules that are involved in the PCOS pathology so we can develop specific diagnostic and management approaches.

Óptimo día de desarrollo embrionario para transferencia en ciclos de reproducción asistida / Optimal day for embryo transfer in assisted reproduction cycles

OBJETIVOS: Comparar los resultados de ciclos de reproducción asistida según la etapa del desarrollo embrionario el día de la transferencia. Ámbito: Pacientes que se someten a ciclos de reproducción asistida del centro de Reproducción Asistida Imar Fertilidad. DISEÑO: Estudio descriptivo observacional retrospectivo. MATERIAL Y MÉTODO: Se incluyen 134 transferencias embrionarias y clasifican en 3 grupos: Grupo 1, embriones en día 2 y día 3 en el momento de la transferencia embrionaria; Grupo 2, embriones en día 4; Grupo 3, embriones en día 5 y día 6 al momento de la transferencia. Se considera que hay diferencia estadística con un valor menor a <0,01 utilizando la prueba de chi cuadrada. RESULTADOS: La tasa de embarazo por grupo es de 32,5%, 51% y 56% para los grupos 1, 2 y 3 respectivamente; no hay diferencias significativas. La tasa de implantación es de 17,5%, 25,8%, 18,91% para los grupos 1, 2 y 3 respectivamente; no se observa significancia estadística. Se pierden el 40,4% de embriones para el grupo 1, el 48,8% en el grupo 2 y el 50% de embriones para grupo 3; no hay diferencias significativas en los grupos comparados. Se vitrifica el 35,4% de embriones en el grupo 1; el 28,6% del grupo 2 y solamente el 13% de embriones para el grupo 3; hay diferencia estadística a favor de los grupos 1 y 2. CONCLUSIONES: Consideramos que los resultados de ciclos de transferencia en mórula pueden ser beneficiosos debido a que logran tasas de embarazo similares a las de blastocisto sin la pérdida embrionaria que conlleva el dejar a cultivo de día 5 estos embriones y a su vez, beneficiándonos de una tasas de criopreservación similar a la de estadios tempranos del desarrollo

OBJECTIVES: To compare results of assisted reproduction cycles according to embryo stage at the moment of the transfer. SETTING: Transfer cycles of an In Vitro Fertilization Program in a Reproduction Assisted center: Imar Fertilidad. DESIGN: Observational retrospective study. MATERIAL AND METHOD: 134 transfer cycles were selected and classified in to three groups: Group 1, Day 2 and Day 3 embryos at the moment of the embryo transfer; Group 2, Day 4 embryos; Group 3, Day 5 and Day 6 embryos at the transfer. Statistical difference is defined as a value of <0.01 after applying the chi square test. RESULTS: The pregnancy rate is 32.5%, 51% y 56% for groups 1, 2 and 3, respectively; there is not statistical difference. Implantation rate is 17.5%, 25.8%, 18.91% for groups 1, 2 and 3, respectively; there is not statistical difference. 40.4% of embryos in group 1 do not qualify for cryopreservation or enter into arrest; 48.8% of group 2 and 50% of embryos of group 3; there is no statistical difference among groups. 35.4% of embryos in group 1 are cryopreserved; 28.6% in group 2 and only 13% of embryos in group 3; there is statistical significance favoring groups 1 and 2. CONCLUSIONS: We consider that day 4 embryo transfer has the advantage of high pregnancy and implantation rates, similar to those of day 5 embryos, plus, the availability of a high number of embryos for cryopreservation, as in day 3 embryo transfers

[Comparison of GnRH agonists and antagonists in an ovular donation program]. / Comparación de agonistas y antagonistas de GnRH en un programa de donación ovular.

INTRODUCTION: GnRH agonists and antagonists are utilized for avoiding premature ovulation in assisted reproductive cycles, (ART) this retrospective study was designed to compare both treatments in controlled ovarian hyperstimulation (HOC) in oocyte donors. MATERIAL AND METHODS: Between Jan99 and Mar03, 141 oocyte donors underwent ART receiving either 0.25 mg daily of a GnRH antagonist (Cetrorelix) from day 6 of stimulation (51 patients) or a long protocol with a GnRH agonist (Leuprolide acetate) (90 patients.) FSHr alone or with HMG or LHr were employed for ovarian stimulation. hCG (Profasi, Serono) was administrated when more than three follicles above 18 mm in diameter were observed, oocyte retrieval was performed 34 hours later. Embryo transfer was performed 3-5 days later. RESULTS: Both groups were homogeneus for age (p=0.142), day 3 FSH (p=0.115), type and total dose of gonadotrophins utilized. There were no significant differences in follicles number (p=0.522), oestradiol levels on the day of hCG (p=0.310) and fertilization rates (p=0.177) The mean number of oocytes retrieved and metaphase II oocytes was significantly lower in GnRH agonist group, (12 vs. 13.9, p=0.05 and 8.6 vs 11; p=0.007) There was no statistical differences in pregnancy and implantation rates between agonist and antagonist groups (52.2% vs 60.8%, 15.1% vs 18.3%; p=0.327 and 0.652). CONCLUSIONS: The high number of metaphase oocytes and the high pregnancy rate observed in the oocyte donors provide evidence that GnRH antagonist does not impair ovarian response, embryo quality or pregnany rates. In oocyte donors cycles the GnRH antagonist is a valid alternative to GnRH agonist, providing the benefit of more flexibility in patient's scheduling.

[Influence of sperm morphology on results of intrauterine insemination]. / Influencia de la morfología espermática en los resultados de inseminación intrauterina.

OBJECTIVE: To determine the influence of sperm morphology, according to WHO criteria, on pregnancy rates of couples who were submitted to intra-uterine insemination (IUI). MATERIAL AND METHODS: Retrospective study that included 787 IUI cycles performed in the Instituto para el Estudio de la Concepción Humana in Monterrey, Mexico, from January to December 2002. Main diagnosis were anovulation, male factor, endometriosis, and cervical factor. All patients were allocated into a controlled ovarian hyperstimulation protocol with either clomiphene citrate, menotropins and/or recombinant FSH. RESULTS: A total of 115 pregnancies were achieved (pregnancy rate per cycle of 14.61%). When seminal parameters were analyzed as independent factors it was found that a motility less than 10%, total motile count after sperm preparation less than 1 million/ml and sperm motility less than 20% had a pregnancy rate of zero. CONCLUSIONS: Patients with normal sperm forms less than 20% according to WHO criteria have no benefit with the IUI and these patients should be canalized to ART.

[Methodology in gynaecological clinical research]. / Metodología de investigación clínica en Ginecología.

Every day the number of published articles in the world wide literature is increased; unfortunately, lot of them lack of a proper research-related methodology and therefore the conclusions might be of less scientific value. Clinicians need to develop their professional exercise based on scientific knowledge and so it is imperative to be familiar with research-related methodology. The present paper offers some tips in order to facilitate the reading and correct interpretation of clinical research.

[Prognostic values of oestradiol/oocyte rate in ICSI patients]. / Pronóstico del indice estradiol-ovulo en la inyección intracitoplasmática de espermatozoides (ICSI).

OBJECTIVES: To analyze the pregnancy rate in women who underwent Intracytoplasmic Sperm Injection (ICSI) program depending of the oestradiol/oocyte index. STUDY DESIGN: Retrospective, comparative. MATERIAL AND METHODS: 332 patients were included. There were divided in three groups depending on the oestradiol/oocyte index: Group A:(100 pg/mL, group B: 101-250 pg/mL and group C: > 250 pg/mL). Therapeutic protocol. Down regulation with leuprolide acetate in late luteal phase protocol, COH with rec-FSH and / or HMG, ultrasonographic and estradiol blood levels were monitored; hCG application when > 3 follicles > 18 mm, oocyte retrieval performed 34 hours later. We analyzed: patient age, male age, number of follicles, estradiol serum levels at the day of hCG application, number of mature oocytes, oestradiol/oocyte index, fertilization rate, transferred embryos, transfer quality, catheter type and luteal support. Statistical analysis (SPSS 11) with chi square, ANOVA and Kruskall-Wallis was used. RESULTS: On having analyzed the number of metaphase II oocytes retrieval, oocytes fertilized and number of transferred embryos among three groups, the best results were obtained in group B. The differences among these variables were significant. (P = 0.014, p = 0.005 and p = 0.003, respectively). When the oestradiol/oocyte index was analyzed and the PR among groups (21.83, 36.62 and 17.80 %) we observed a significant difference (p = 0.003). CONCLUSION: It is convenient to monitor the oestradiol blood levels to offer schemes of COH less aggressive to improve the oocyte quality. The oestradiol/oocyte index is a parameter adapted as a predictive value of pregnancy.

[High concentrations of serum estradiol in assisted reproduction]. / Altas concentraciones de estradiol sérico en reproducci6ón asistida.

OBJECTIVES: To analyze the influence of the levels of estradiol on the day of HCG in the pregnancy rate (PR) of ICSI and oocyte donation. STUDY DESIGN: Retrospective, comparative. MATERIAL AND METHODS: 333 patients underwent ICSI and 66 in oocyte donation were included dividing them according to the level of estradiol: a) < 1,000 pg/mL, b) 1,001-3,000 pg/mL and c) > 3,000 pg/mL. Therapeutic protocol: Down regulation with acetate leuprolide in late luteal phase, COH with FSHr and/or HMG, ultrasonographic monitoring and estradiol blood levels, HCG application with > 3 follicles > 18 mm, oocyte retrieval 34 hours later. We analyzed: PR, age (including receptors), FSH and LH. Number, mature grade and fertilized oocytes; luteal support, transfer quality and type of catheter. Statistical analysis (SPSS 11) with chi square, ANOVA and Kruskall-Wallis. RESULTS: ICSI: Older patients in group A (p < 0.001), but without difference between B and C groups (p = 0.08). Statistical difference in number of follicles, number of oocytes, fertilized oocytes and transferred embryos being less in the A group (p < 0.001). Statistical difference in PR 21.7, 35.6 and 25.7% in A, B and C groups respectively (p = 0.032). Oocyte donation: Group A has younger patients (p = 0.005), FSH and LH were similiar among groups. Major number of follicles were observed to increase estradiol levels, but major quantity of metaphase II and fertilized oocytes were observed in group B (p = 0.05). PR without significant differences: 50, 51.5 and 52.3% in groups A, B and C (p = 0.977). Without statistical difference in the age of receptors; transferred embryos, type of catheter and quality on ICSI and oocyte donation groups. CONCLUSION: High estradiol levels at the day of HCG application affect the PR in patients submitted to ICSI. The best results were obtained with estradiol levels between 1,000 and 3,000 pg/mL. In oocyte donation the high concentrations of estradiol do not affect the PR of the receptors.