Elevated progesterone on the trigger day does not impair the outcome of Human Menotrophins Gonadotrophin and Medroxyprogesterone acetate treatment cycles.

To demonstrate the incidence and effects of elevated progesterone (P) on the trigger day on the outcome of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using Medroxyprogesterone acetate (MPA) co-treated with Human Menotrophins Gonadotrophin (hMG + MPA), we performed a retrospective analysis including 4106 IVF/ICSI cycles. The cycles were grouped according to the P level on the trigger day: <1 ng/mL, between 1-1.5 ng/ml (including 1), between 1.5-2 ng/mL (including 1.5), and ≥2 ng/mL. The primary outcome measure was live birth rate. The prevalence of P level categories was 12.93% (531/4106), 2.92% (120/4106), and 1.92% (79/4106) in women with P between 1-1.5 ng/mL, between 1.5-2 ng/mL, and ≥2 ng/mL, respectively. The mean stimulation duration, total hMG dose, serum follicle stimulating hormone (FSH), estrogen(E2) on the trigger day and the number of oocytes in patients with elevated P were significantly higher than patients with P < 1 ng/mL (P < 0.05). However, there were no significant differences in the oocyte retrieval rates, fertilization rates, implantation rates, clinical pregnancy rates and live birth rates between the groups based on frozen embryo transfer (FET). We concluded that elevated P on the trigger day had no negative effect on the final outcome of the hMG + MPA treatment cycles based on FET.

Influence of severe endometriosis on gene expression of vascular endothelial growth factor and interleukin-6 in granulosa cells from patients undergoing controlled ovarian hyperstimulation for in vitro fertilization-embryo transfer.

OBJECTIVE: To evaluate how endometriosis affects expression of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in granulosa cells. DESIGN: Prospective study. SETTING: IVF-ET program at Osaka Medical College. PATIENT(S): Seventeen patients with revised American Fertility Society stage IV endometriosis and 17 patients with tubal infertility and no endometriosis. INTERVENTION(S): Granulosa cells obtained at oocyte retrieval were examined for VEGF and IL-6 gene expression. MAIN OUTCOME MEASURE(S): Serum E(2) and P levels at hCG administration, number of oocytes, fertilization rate, high-quality embryo rate, and pregnancy rate, and expression of VEGF and IL-6 genes. RESULT(S): Total hMG and FSH levels were statistically significantly higher in patients with endometriosis; however, the number of retrieved oocytes and the fertilization rate were lower compared with patients with tubal infertility. Serum E(2) levels and expression of VEGF in patients with tubal infertility were statistically significantly higher than those in patients with endometriosis. Interleukin-6 gene expression did not differ between the groups. CONCLUSION(S): In severe endometriosis, lower VEGF gene expression in granulosa cells may adversely affect oocyte development and maturation.

Modulation of folliculogenesis and steroidogenesis in women by graded menotrophin administration.

BACKGROUND: To test the effects of progressively decreasing dosages of exogenous LH we combined various amounts of HMG, containing FSH, LH and HCG, and highly purified (HP) FSH to treat 120 GnRH agonist-suppressed infertile female patients as candidates for controlled ovarian stimulation (COS). METHODS: Subjects were randomly assigned to four treatment groups that received the following daily i.m. gonadotrophin regimens: A, FSH 150 IU only; B, FSH 150 IU and LH activity 37.5 IU; C, FSH 150 IU and LH activity 75 IU; D, FSH 150 IU and LH activity 150 IU. FSH dose adjustments were allowed only after the 14th treatment day. Monitoring included transvaginal ultrasound at 2-day intervals and daily determinations of LH, FSH, estradiol (E(2)), progesterone, testosterone and HCG. RESULTS: Duration of COS was significantly shortened in patients receiving at least 75 IU daily of LH activity. Small (<10 mm diameter) pre-ovulatory ovarian follicle occurrence was inversely correlated with LH activity dose administered (r = -0.648, P < 0.0001) and serum HCG levels (r = -0.272, P < 0.01) but not to serum LH levels. Serum testosterone levels were positively correlated to the LH activity dose administered (r = 0.313, P < 0.001), while serum progesterone levels were positively correlated to the FSH dose administered (r = 0.447, P < 0.00001) but not to the LH activity dose administered. CONCLUSIONS: Firstly, HCG content considerably contributes to HMG activity; secondly, menotrophin LH activity content can reduce in a dose-dependent manner the occurrence of small pre-ovulatory follicles; and finally, contrary to common belief, enhanced FSH stimulation rather than LH activity appears to cause premature follicle luteinization during COS.

Minimal requirements for a successful outcome in anovulatory patients treated with human menopausal gonadotropins.

OBJECTIVE: To determine the minimal requirements for achieving a full-term singleton pregnancy in hMG-treated patients. METHODS: One hundred and ninety-two pregnancy cycles resulting from hMG therapy in infertile patients were retrospectively studied to determine the minimal requirements for the occurrence of a pregnancy in those women. The cycles were divided into five groups: pregnancies ending in miscarriage, ectopic pregnancies, pregnancies ending in preterm delivery, full-term singleton pregnancies, and full-term multiple pregnancies. The number of hMG ampules, the number of preovulatory follicles reaching 18 mm or more in diameter, the cervical mucus score (Insler), the number of living spermatozoa per high-power field (HPF) observed in the cervical mucus on the day of hCG administration, and the midluteal plasma progesterone concentration were determined and correlated with the outcome of the pregnancy in the five groups studied. The minimal requirements for the occurrence of a full-term singleton pregnancy were also determined. RESULTS: In this cohort of 192 women, the mean number of hMG ampules administered was 25.38 (1903.5 IU), the mean number of preovulatory follicles reaching 18 mm was 2.1, the mean cervical mucus score (Insler) was 9.48, and the mean number of motile spermatozoa per HPF in the cervical mucus on the day of hCG administration was 19.3. There were no statistically significant differences between the five groups studied regarding these four variables. The mean midluteal plasma progesterone concentration was 29.07 ng/mL and there was no statistically significant difference in midluteal plasma progesterone concentration between the cycles resulting in full-term deliveries and those ending in miscarriage. However, a statistically significant difference in midluteal plasma progesterone concentration was found between the cycles resulting in full-term singleton pregnancies and those resulting in full-term multiple pregnancies. CONCLUSIONS: The minimal requirements for achieving a full-term singleton pregnancy were 9 ampules of hMG (675 IU), one 18-mm follicle, a cervical mucus score (Insler) of 6 on the day of hCG administration, and a midluteal plasma progesterone concentration of 10.83 ng/mL. The presence of motile spermatozoa in the cervical mucus was a reassuring sign in 92.7% of instances but was not an absolute necessity for a successful outcome.

Pharmacokinetics of exogenous gonadotropin and ovarian response in in vitro fertilization.

OBJECTIVE: To assess the diffusion of gonadotropin into the follicular fluid (FF) and its relation to the results achieved in a human IVF-ET program. DESIGN: Retrospective pharmacokinetic study. SETTING: Fukuoka University Hospital, Japan. PATIENT(S): Eighty-seven infertile patients underwent 137 cycles of IVF-ET. INTERVENTION(S): Serum and FF were collected at the time of oocyte recovery. The hCG ratio (between follicular hCG and serum hCG concentrations, measured by time-resolved fluoroimmunoassay) was evaluated as an index of the diffusion of exogenous gonadotropin. MAIN OUTCOME MEASURE(S): Relation between hCG ratio and the results and outcome of the IVF-ET program. RESULT(S): The hCG ratio decreased with the total dosage of hMG and increased with the serum E2 level, the number of oocytes recovered, and the number of oocytes fertilized. Patients with a poor response showed a low hCG ratio, which was associated with a complete lack of fertilization. The mean hCG ratio in the pregnant cycles was significantly higher than that in the nonpregnant cycles. An hCG ratio > 0.46 was seen in all pregnant cycles. CONCLUSION(S): The diffusion of exogenous gonadotropin into the FF may be an important predictor of IVF outcome.

Características generales y hormonas de la reproducción en la mujer posmenopausica / General characteristics and reproduction hormones of post-menopausal women

Se seleccionó una muestra aleatoria triste de 134 mujeres posmenopáusicas de un área de salud urbana, para conocer algunas características generales, así como las concentraciones de la hormonas de la reproducción (gonadotropinas hipofisarias y sexoesteroides), en este período de la vida. Se determinaron por radioinmunoanálisis las siguientes hormonas : FSH, LH, estradiol (E2), testosterona (T), androstenediona (A'd), prolactina (PRL) y el precursor 17 hidroxiprogesterona (17 OH-P). La edad cronólogica media de las mujeres fue de 56,3 años y un promedio de 8,4 años desde la menopausia. La edad de la menopausia fue 48,1 ñ 4,7 años, fue poco frecuente después de los 55 años (2,2 por ciento) y antes de los 40 (7,5 por ciento); no se presentó ningún caso de menopausia precoz. La obesidad y el hábito de fumar son hallazgos comunes en la mujer posmenopáusica, ambos son factores de riesgo de trastornos de alta prevalencia en estas mujeres como son las cardiopatías isquémicas y la hipertensión arterial, por lo cual se obvia la necesidad de insistir e eliminar o disminuir el riesgo. El patrón de las hormonas de la producción en las mujeres posmenopáusicas se caracterizó por niveles elevados de gonadotropinas (FSH y LH), índice LH/FSH normal, niveles disminuidos de E2 y niveles normales de PRL, 17 OH-P y andrógenos (Ty A'd)

Características generales y hormonas de la reproducción en la mujer posmenopausica / General characteristics and reproduction hormones of post-menopausal women

Se seleccionó una muestra aleatoria triste de 134 mujeres posmenopáusicas de un área de salud urbana, para conocer algunas características generales, así como las concentraciones de la hormonas de la reproducción (gonadotropinas hipofisarias y sexoesteroides), en este período de la vida. Se determinaron por radioinmunoanálisis las siguientes hormonas : FSH, LH, estradiol (E2), testosterona (T), androstenediona (A'd), prolactina (PRL) y el precursor 17 hidroxiprogesterona (17 OH-P). La edad cronólogica media de las mujeres fue de 56,3 años y un promedio de 8,4 años desde la menopausia. La edad de la menopausia fue 48,1 ñ 4,7 años, fue poco frecuente después de los 55 años (2,2 por ciento) y antes de los 40 (7,5 por ciento); no se presentó ningún caso de menopausia precoz. La obesidad y el hábito de fumar son hallazgos comunes en la mujer posmenopáusica, ambos son factores de riesgo de trastornos de alta prevalencia en estas mujeres como son las cardiopatías isquémicas y la hipertensión arterial, por lo cual se obvia la necesidad de insistir e eliminar o disminuir el riesgo. El patrón de las hormonas de la producción en las mujeres posmenopáusicas se caracterizó por niveles elevados de gonadotropinas (FSH y LH), índice LH/FSH normal, niveles disminuidos de E2 y niveles normales de PRL, 17 OH-P y andrógenos (Ty A'd)

A prospective randomized study on oestradiol valerate supplementation in addition to intravaginal micronized progesterone in buserelin and HMG induced superovulation.

A prospective randomized study was conducted to evaluate the use of adding oestradiol valerate 6 mg per os daily to intravaginal micronized progesterone (600 mg daily) as luteal supplements. The study comprised 378 infertile women superovulated with a gonadotrophin releasing-hormone agonist (GnRHa) and human menopausal gonadotrophins (HMG) for in-vitro fertilization (IVF) or zygote intra-Fallopian transfer (ZIFT). The clinical pregnancy rate was similar (29%) whether or not oestradiol valerate was added to intravaginal progesterone. Eighteen out of twenty-two endometrial biopsies were in phase, and morphological evaluations of the two luteal supplementation groups were not different. Serum hormone profiles in singleton pregnancies showed a similar day of appearance of human chorionic gonadotrophin (HCG) in both protocols but significantly lower oestradiol concentrations arose in the group without oestradiol valerate. In 32% of the singleton pregnancies, the first appearance of HCG occurred later than day 12 after HCG injection; in those ongoing pregnancies, corpus luteum rescue--as measured by significantly lower serum oestradiol and progesterone concentrations--was compromised. This study provided no evidence of any benefit of routinely supplementing GnRHa/HMG cycles with oestradiol valerate in addition to intravaginal micronized progesterone.

Endocrine changes and follicular development in patients during ovulation induction using Goserelin and different gonadotropin treatments.

The aim of this study was to compare endocrine changes and the follicular development in patients receiving pure FSH alone or in association with LH after desensitization with an LH-RH agonist depot. Thirty four cycles were selected for this prospective randomized study. Desensitization was obtained using Goserelin the cycle before the stimulation. Induction of ovulation for IUI was carried out with 225 IU/day of pure FSH or with 225 IU/day of hMG. The number of days and ampules required for follicular maturation were equivalent in the two groups. The same number of follicles were developed, while different, but not significant, pregnancy rates were obtained. Estradiol values at the end of stimulation were significantly lower for FSH group. In conclusion the contemporary administration of LH with FSH does not exert any effect on follicular development, but it seems to facilitate E2 synthesis, probably providing more substrate for the aromatization process.

Teste do progestogenio e niveis de gonadotrofinas em mulheres na pos-menopausa / Progestogen test and gonadotropins levels in post-menopausal women

Foram estudadas 79 mulheres pos-menopausais na Clinica Ginecologica da Faculdade de Medicina da Universidade de Sao Paulo com o objetivo de avaliar o teste do progestogenio correlacionando-o com os niveis de gonadotropinas, e os indices menopausal de Kupperman e Quetelet. A media etaria foi 51,4 anos e a media do tempo de menopausa foi 3,6 anos. As pacientes foram divididas em 2 grupos: A e B. O grupo A, composto por 49 pacientes, recebeu acetato de medroxiprogesterona 5mg/dia durante 10 dias. O grupo B com 30 mulheres, recebeu alilesterol na dose de 5mg/dia, durante 10 dias. Os resultados revelaram que os testes de progestogenio foi positivo em 16 pacientes do grupo A e 1 do grupo B. A media do tempo de menopausa foi 1,6 e 4,2 anos, nos grupos A e B, respectivamente. O indice menopausal de Kupperman nao mostrou correlacao com a positividade do teste, mas o indice de Quetelet revelou que houve maior percentual da positividade do teste quando o indice esteve acima de 30.

Respuesta hipofisaria a la hormona liberadora de gonadotropinas (LHRH) en pacientes con hiperlipoproteinemia primaria / Hypophyseal response to luteinizing hormone relesing hormone in patients with primary hyperlipoproteinemia

Se estudió la respuesta gonadotrópica a la hormona liberadora de gonadotropinas en 12 pacientes con hiperlipoproteinemia primaria. Se compararon los resultados con los obtenidos en un grupo control de hombres normales, la evaluación estadística se realizó por medio del análisis de varianza y la prueba t de Student. Se constató una respuesta exagerada de la hormona foliculoestimulante a la LHRH, lo cual sugiere que en estos pacientes existe un daño testicualr primario al nivel de los tubos seminíferos. La respuesta de la hormona luteinizante fue similar en los pacientes y en los controles. Los resultados indican que en los pacientes con hiperlipoproteinemia primaria, la reserva gonadotrópica hipofisaria está conservada y en ellos parece existir un daño primario de los tubos seminíferos

Respuesta hipofisaria a la hormona liberadora de gonadotropinas (LHRH) en pacientes con hiperlipoproteinemia primaria / Hypophyseal response to luteinizing hormone relesing hormone in patients with primary hyperlipoproteinemia

Se estudió la respuesta gonadotrópica a la hormona liberadora de gonadotropinas en 12 pacientes con hiperlipoproteinemia primaria. Se compararon los resultados con los obtenidos en un grupo control de hombres normales, la evaluación estadística se realizó por medio del análisis de varianza y la prueba t de Student. Se constató una respuesta exagerada de la hormona foliculoestimulante a la LHRH, lo cual sugiere que en estos pacientes existe un daño testicualr primario al nivel de los tubos seminíferos. La respuesta de la hormona luteinizante fue similar en los pacientes y en los controles. Los resultados indican que en los pacientes con hiperlipoproteinemia primaria, la reserva gonadotrópica hipofisaria está conservada y en ellos parece existir un daño primario de los tubos seminíferos

Comparison of implantation and early development of human embryos fertilized in vitro versus in vivo using transvaginal ultrasound.

Several reports in the literature suggest delayed implantation of in vitro-fertilized human embryos compared to in vivo-fertilized eggs. The use of high-frequency transvaginal transducers for early detection of pregnancy has allowed the identification of the gestational sac with very low serum human chorionic gonadotropin (beta-hCG) levels. Thus, the present study evaluated whether retarded implantation can be identified using this novel technology. We studied 13 single pregnancies after in vitro fertilization (IVF) and 14 pregnancies after artificial insemination either by husband (n = 6) or donor (n = 8). In the IVF patients, oocytes were retrieved 35 hours after hCG administration. Embryo transfer occurred approximately 48 hours after retrieval. Artificial insemination was performed 24 and 48 hours after hCG administration. Transvaginal ultrasound scans and serum beta-hCG levels were evaluated every 3 days starting day 12 post-hCG administration. Serum beta-hCG levels rose in parallel when in vitro- and in vivo-fertilized embryos were compared. Similarly, there was no difference between groups in the mean time needed to detect early embryonic structures, such as the embryonic sac, yolk sac, and heartbeats, or the growth rate of the gestational sac. In conclusion, there was no difference in detecting implantation and early embryonic development of human embryos fertilized in vivo versus in vitro as ascertained by ultrasound scans and serum beta-hCG levels. An embryonic sac is detected 23-24 days after hCG administration in pregnancies achieved by assisted reproductive techniques.

Pacientes con angiopatía obliterante de miembros inferiores y disfunción sexual / Patients with obliterant angiopathy of the lower extremities and sexual dysfunction

Se estudiaron 24 pacientes masculinos con lesiones arterioscleróticos de miembros inferiores, diagnosticados radiológicamente. A todos se les realizó una prueba de estimulación con gonadotropina coriónica humana (hCG) y se les determinó la concentración basal a las 24, 48, 72-96 horas después de administrada la hCG, de testosterona (T), el estradiol (E2), la hormona foliculo estimulante (FSH), y la lutenizante (LH). Los pacientes se agruparonm en respondedores (R); los que duplicaron al menos la concentración basal de T a las 24 horas, y los no respondedores (NR): en los casos en que la elevación de T a las 24 horas fue inferior al 50% de la cifra basal. Se les realizó un examen con ultrasonografía Doppler para evaluar el flujo sanguíneo del pene, y se estabilizó el índice pene/brazo. Se conoció el estado de la líbido, eyaculación y de la potencia sexual, mediante interrogatorio. La impotencia sexual fue referida por más del 50% de los pacientes. En el grupo NR el índice pene/brazo fue significativamente inferior al considerado como normal. La concentración media de T plasmática fue inferior al tomado como normal, el E2 no fue diferente. Los casos con valores elevados de FSH se encontraron en el grupo de los NR, así como el índice pene/brazo fue inferior al normal. Casi todos los enfermos con FSH elevada, tenían también la LH. Los trastornos arterioscleróticos de miembros inferiores, están asociados a un cierto daño de la función testicular, que se expresa con disminución plasmática de T, incapacidad de respuesta testicular a la hCG, y niveles elevados de FSH/LH, asociados a algunos trastornos de la libido, potencia sexual o de la eyaculación

Pacientes con angiopatía obliterante de miembros inferiores y disfunción sexual / Patients with obliterant angiopathy of the lower extreities and sexual dysfunction

Se estudiaron 24 pacientes masculinos con lesiones arterioscleróticos de miembros inferiores, diagnosticados radiológicamente. A todos se les realizó una prueba de estimulación con gonadotropina coriónica humana (hCG) y se les determinó la concentración basal a las 24, 48, 72-96 horas después de administrada la hCG, de testosterona (T), el estradiol (E2), la hormona foliculo estimulante (FSH), y la lutenizante (LH). Los pacientes se agruparonm en respondedores (R); los que duplicaron al menos la concentración basal de T a las 24 horas, y los no respondedores (NR): en los casos en que la elevación de T a las 24 horas fue inferior al 50

de la cifra basal. Se les realizó un examen con ultrasonografía Doppler para evaluar el flujo sanguíneo del pene, y se estabilizó el índice pene/brazo. Se conoció el estado de la líbido, eyaculación y de la potencia sexual, mediante interrogatorio. La impotencia sexual fue referida por más del 50

de los pacientes. En el grupo NR el índice pene/brazo fue significativamente inferior al considerado como normal. La concentración media de T plasmática fue inferior al tomado como normal, el E2 no fue diferente. Los casos con valores elevados de FSH se encontraron en el grupo de los NR, así como el índice pene/brazo fue inferior al normal. Casi todos los enfermos con FSH elevada, tenían también la LH. Los trastornos arterioscleróticos de miembros inferiores, están asociados a un cierto daño de la función testicular, que se expresa con disminución plasmática de T, incapacidad de respuesta testicular a la hCG, y niveles elevados de FSH/LH, asociados a algunos trastornos de la libido, potencia sexual o de la eyaculación

[Treatment of ovarian polycystic syndrome in vitro. Physiopathogenetic considerations]. / Traitement des dystrophies ovariennes polykystiques au cours de fécondation in vitro. Considerations physiopathogeniques.

More than 60% of patients with polycystic ovary disease (PCO) cannot conceive after repeated ovulation inductions with Clomifene citrate although there is ovulation or more frequently follicle luteinization. Because of hyperstimulation, therapy with hMG has been superseded by low doses of purified FSH with variable results according to authors. It has been even claimed that there was no benefit to replace hMG with FSH. However, on the basis of the PCO physico-pathology, namely LH hypersecretion and androgen hyperproduction, it would be rational to associate the desensitization of the pituitary with LH-RH agonist and the ovary stimulation with variable doses of hMG or purified FSH. In the series where such therapy associating LH-RH agonists with purified FSH was applied, the results concerning suppression of LH and androgen secretion, and the occurrence of pregnancy were interesting. However, the risk of hyperstimulation still occurred. Thus, the first part concerns the critical review of these results while, in the second part, our experience in in vitro fecundation will be reported.

Follicle growth curves and hormonal patterns in patients with the luteinized unruptured follicle syndrome.

A prospective longitudinal and standardized study is presented, dealing with ultrasonographic and hormonal characteristics of the luteinized unruptured follicle (LUF) syndrome. Among 600 cycles monitored in 270 infertility patients, 40 cycles in 27 patients showed no evidence of follicle rupture, in spite of signs of luteinization, as reflected by basal body temperature recordings and progesterone determinations. In this study, 20 LUF cycles in 20 infertile patients were compared with 45 ovulatory cycles in 45 control women. During the follicular phase, no substantial difference in follicle growth was found, but after the luteinizing hormone peak, LUF follicles, instead of rupturing, showed a typical accelerated growth pattern. Both mean luteinizing hormone peak levels and midluteal progesterone levels were significantly lower in LUF cycles than in the control cycles. However, the duration of the luteal phase was not affected. Both central and local factors can be held responsible for the lack of follicle rupture. Ultrasound offers new possibilities as a noninvasive method in diagnosing the LUF syndrome.

Endocrine profiles of patients with testicular tumors treated with radiotherapy.

Blood samples for hormone analysis were obtained 5 to 20 years post-therapy from 12 men with testicular tumors who were originally treated by unilateral orchiectomy followed by abdominal and/or pelvic irradiation. In nine patients (75%) the levels of FSH and LH, and in one patient (8%) the testosterone values, were outside the ranges found in age- and sex-matched controls. From this retrospective study we conclude that, even when the remaining testis is kept outside the field of radiation, significant radiation damage occurs, mainly through scatter. This damage is more likely to occur if the hemiscrotum is irradiated. Methods of shielding are available to reduce the dose received by the contralateral testis.