RESUMEN
Human menopausal gonadotropin (hMG) has LH activity, and it may have beneficial effects in terms of oocyte quality and endometrial receptivity similar to recombinant LH supplementation. The aim of this study was to assess the effects of hMG, and its commencement time on the outcome of assisted reproductive technology (ART) cycles of POSEIDON group 3 and 4 poor responders. Data of 558 POSEIDON group 3 and 4 poor responders who underwent ART treatment following a GnRH antagonist cycle at a university-based infertility clinic between January 2014 and December 2019 were reviewed. hMG was commenced at the early follicular phase or mid-follicular phase in the study groups. The control group did not receive hMG stimulation. Live birth rate (LBR) was the main outcome measure. The mean duration of stimulation was significantly shorter in early follicular hMG group than in mid-follicular hMG group (11.9 ± 3.6 days vs. 12.8 ± 4 days, respectively; P = 0.027). The mean numbers of oocytes retrieved and MII oocytes were comparable between the groups. The LBRs per embryo transfer in early follicular hMG, mid-follicular hMG, and control groups were 21.9%, 11.7%, and 11.6%, respectively (P = 0.035). In conclusion, there is a significant association between the commencement time of hMG and live birth chance in ART cycles of POSEIDON group 3 and 4 poor responders. Early initiation of hMG together with rFSH seems to be beneficial in this specific population.
Asunto(s)
Fármacos para la Fertilidad Femenina/administración & dosificación , Infertilidad/terapia , Menotropinas/administración & dosificación , Ovario/efectos de los fármacos , Inducción de la Ovulación , Ovulación/efectos de los fármacos , Adulto , Esquema de Medicación , Quimioterapia Combinada , Femenino , Fármacos para la Fertilidad Femenina/efectos adversos , Hormona Folículo Estimulante/administración & dosificación , Humanos , Infertilidad/diagnóstico , Infertilidad/fisiopatología , Nacimiento Vivo , Menotropinas/efectos adversos , Ovario/fisiopatología , Inducción de la Ovulación/efectos adversos , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Inyecciones de Esperma Intracitoplasmáticas , Resultado del TratamientoRESUMEN
None of the models developed in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is sufficiently good predictors of pregnancy. The aim of this study was to determine whether ratios between prognostic factors could predict the clinical pregnancy rate in IVF/ICSI. We analyzed IVF/ICSI cycles (based on long GnRH agonist-FSH protocols) at two ART centers (the second to validate externally the data). The ratios studied were (i) the total FSH dose divided by the serum estradiol level on the hCG trigger day, (ii) the total FSH dose divided by the number of mature oocytes, (iii) the serum estradiol level on the trigger day divided by the number of mature oocytes, (iv) the serum estradiol level on the trigger day divided by the endometrial thickness on the trigger day, (v) the serum estradiol level on the trigger day divided by the number of mature oocytes and then by the number of grade 1 or 2 embryos obtained, and (vi) the serum estradiol level on the trigger day divided by the endometrial thickness on the trigger day and then by the number of grade 1 or 2 embryos obtained. The analysis covered 2421 IVF/ICSI cycles with an embryo transfer, leading to 753 clinical pregnancies (31.1% per transfer). Four ratios were significantly predictive in both centers; their discriminant power remained moderate (area under the receiver operating characteristic curve between 0.574 and 0.610). In contrast, the models' calibration was excellent (coefficients: 0.943-0.978; p < 0.001). Our ratios were no better than existing models in IVF/ICSI programs. In fact, a strongly discriminant predictive model will be probably never be obtained, given the many factors that influence the occurrence of a pregnancy.
Asunto(s)
Fármacos para la Fertilidad Femenina/administración & dosificación , Fertilización In Vitro , Hormona Folículo Estimulante/administración & dosificación , Hormona Liberadora de Gonadotropina/agonistas , Infertilidad/terapia , Menotropinas/administración & dosificación , Inducción de la Ovulación , Ovulación/efectos de los fármacos , Adolescente , Adulto , Biomarcadores/sangre , Esquema de Medicación , Quimioterapia Combinada , Transferencia de Embrión , Estradiol/sangre , Femenino , Fármacos para la Fertilidad Femenina/efectos adversos , Fertilización In Vitro/efectos adversos , Hormona Folículo Estimulante/efectos adversos , Humanos , Infertilidad/sangre , Infertilidad/diagnóstico , Infertilidad/fisiopatología , Masculino , Menotropinas/efectos adversos , Persona de Mediana Edad , Inducción de la Ovulación/efectos adversos , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Inyecciones de Esperma Intracitoplasmáticas , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of highly purified human menotropin (HP-hMG) and recombinant follicle-stimulating hormone (rFSH) for controlled ovarian stimulation in a population of patients predicted to be high responders. DESIGN: Randomized, open-label, assessor-blinded, parallel-group, noninferiority trial. SETTING: Fertility centers. PATIENT(S): A total of 620 women with serum antimüllerian hormone (AMH) ≥5 ng/mL. INTERVENTION(S): Controlled ovarian stimulation with HP-hMG or rFSH in a GnRH antagonist assisted reproductive technology (ART) cycle. Fresh transfer of a single blastocyst was performed unless ovarian response was excessive, in which all embryos were cryopreserved. Subjects could undergo subsequent frozen blastocyst transfer within 6 months of randomization. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate (OPR) after fresh transfer (primary endpoint), as well as cumulative live birth, ovarian hyperstimulation syndrome (OHSS), and pregnancy loss rates. RESULTS: OPR/cycle start after fresh transfer was 35.5% with HP-hMG and 30.7% with rFSH (difference: 4.7%, 95% CI -2.7%, 12.1%); noninferiority was established. Compared to rFSH, HP-hMG was associated with significantly lower OHSS (21.4% vs. 9.7% respectively; difference: -11.7%, 95% CI -17.3%, -6.1%) and cumulative early pregnancy loss rates (25.5% vs. 14.5% respectively; difference: -11.0%, 95% CI -18.8%, -3.14%). Despite 43 more transfers in the rFSH group, cumulative live birth rates were similar with HP-hMG and rFSH at 50.6% and 51.5% respectively (difference: -0.8%, 95% CI -8.7%, 7.1%). CONCLUSION(S): In high responders, HP-hMG provided comparable efficacy to rFSH with fewer adverse events, including pregnancy loss, suggesting its optimized risk/benefit profile in this population. CLINICAL TRIAL REGISTRATION NUMBER: NCT02554279 (clinicaltrials.gov).
Asunto(s)
Fármacos para la Fertilidad Femenina/uso terapéutico , Hormona Folículo Estimulante Humana/uso terapéutico , Infertilidad/terapia , Menotropinas/uso terapéutico , Ovario/efectos de los fármacos , Inducción de la Ovulación , Ovulación/efectos de los fármacos , Inyecciones de Esperma Intracitoplasmáticas , Aborto Espontáneo/etiología , Adulto , Hormona Antimülleriana/sangre , Biomarcadores/sangre , Femenino , Fertilidad , Fármacos para la Fertilidad Femenina/efectos adversos , Hormona Folículo Estimulante Humana/efectos adversos , Humanos , Infertilidad/diagnóstico , Infertilidad/fisiopatología , Nacimiento Vivo , Masculino , Menotropinas/efectos adversos , Síndrome de Hiperestimulación Ovárica/inducido químicamente , Ovario/fisiopatología , Inducción de la Ovulación/efectos adversos , Embarazo , Índice de Embarazo , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico , Transferencia de un Solo Embrión , Inyecciones de Esperma Intracitoplasmáticas/efectos adversos , Resultado del Tratamiento , Estados Unidos , Adulto JovenRESUMEN
Some of the common side effects of the injectable gonadotropins, used during fertility treatments, are pain at the injection site, skin erythema, muscle pain, and rarely vasovagal reflex. These side effects cause inconvenience and lower patient's tolerance for fertility treatments.The purpose of this study was to evaluate the safety and efficacy of an FDA-approved dose of nasal human menopausal gonadotropins (Menopur) in women undergoing fertility treatment. Healthy regularly cycling reproductive-aged women (n=4) with infertility were enrolled. A total of 75 IU of each Menopur bottle was dissolved and placed in a nasal pump spray device (concentration of 3.75 IU/spray). Each participant was allowed to inhale a total of 2 sprays daily after which ovarian response during the follicular phase was monitored by transvaginal ultrasound and serum hormone measurement. None of the participants reported any side effects at the nasal site of drug administration. No known common side effects of the Menopur drug were reported by any of the participants. Despite adequate absorption of the nasal Menopur, as confirmed by elevated serum FSH levels while taking the nasal medication, 3 out of 4 participants did not show any follicular growth until cycle day 13 while only one participant who agreed to continue taking the medication until cycle day 20 developed one dominant follicle and had elevated serum estradiol levels. This FDA approved case series suggest that nasal route of Menopur administration seems to be safe at a very low doses and it constitutes a potential novel approach for ovarian stimulation.
Asunto(s)
Administración Intranasal , Fármacos para la Fertilidad Femenina , Fertilización In Vitro , Menotropinas , Adulto , Femenino , Fármacos para la Fertilidad Femenina/administración & dosificación , Fármacos para la Fertilidad Femenina/efectos adversos , Fármacos para la Fertilidad Femenina/farmacología , Fármacos para la Fertilidad Femenina/uso terapéutico , Humanos , Infertilidad Femenina/tratamiento farmacológico , Menotropinas/administración & dosificación , Menotropinas/efectos adversos , Menotropinas/farmacología , Menotropinas/uso terapéutico , Rociadores Nasales , Folículo Ovárico/efectos de los fármacos , Inducción de la OvulaciónRESUMEN
BACKGROUND: Progress in vitrification techniques has allowed reproductive physicians to consider new strategies for using progestin as an alternative to a GnRH analogue to improve in vitro fertilisation (IVF). However, the role of progestin in blocking luteinising hormone (LH) surges and its potential in clinical practice are unclear, especially for poor responders. We designed a prospective randomised controlled trial (RCT) to compare the efficacy of a gonadotropin-releasing hormone (GnRH) antagonist and progestin in blocking LH surges and premature ovulation in poor responders. METHODS/DESIGN: Poor responders who meet the Bologna criteria will be randomised to one of two stimulation regimens-gonadotropin-releasing hormone (GnRH) antagonist or progestin-primed ovarian stimulation (PPOS)-using a computer-generated random number. Fresh embryos were transferred in the GnRH antagonist group and frozen embryos were transferred in the PPOS group. The primary outcome is the incidence of premature LH surges. Secondary outcomes include the number of oocytes retrieved, the number of embryos available for transfer, implantation rates and clinical pregnancy. The sample size for this trial is estimated as 340 participants, with 170 participants in each group. The data analysis will be by intention to treat. DISCUSSION: To our knowledge, this is the first RCT to examine the efficacy of administering progestin orally to block LH surges and premature ovulation compared with the GnRH antagonist protocols in poor responders undergoing IVF treatment. TRIAL REGISTRATION: www.chictr.org.cn . ChiCTR-IPR-17010906 . Registered on 18 March 2017.
Asunto(s)
Fármacos para la Fertilidad Femenina/administración & dosificación , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Infertilidad/tratamiento farmacológico , Hormona Luteinizante/sangre , Acetato de Medroxiprogesterona/administración & dosificación , Menotropinas/administración & dosificación , Inducción de la Ovulación/métodos , Ovulación/efectos de los fármacos , Congéneres de la Progesterona/administración & dosificación , Inyecciones de Esperma Intracitoplasmáticas , Administración Oral , Adulto , Biomarcadores/sangre , China , Protocolos Clínicos , Criopreservación , Implantación del Embrión , Transferencia de Embrión , Femenino , Fármacos para la Fertilidad Femenina/efectos adversos , Humanos , Infertilidad/sangre , Infertilidad/diagnóstico , Infertilidad/fisiopatología , Masculino , Acetato de Medroxiprogesterona/efectos adversos , Menotropinas/efectos adversos , Recuperación del Oocito , Inducción de la Ovulación/efectos adversos , Embarazo , Índice de Embarazo , Congéneres de la Progesterona/efectos adversos , Estudios Prospectivos , Proyectos de Investigación , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Human menopausal gonadotropin (HMG) is one of the commonest drugs used for ovarian stimulation with no reports on the audio-vestibular system. This study aims to examine HMG on the hearing profile of patients planning intracytoplasmic sperm injection (ICSI). METHODS: This prospective study was conducted from June 2016 to June 2017 in a tertiary referral hospital. The audio-vestibular system of a total of 30 patients was evaluated using pure tone audiometry, distortion product otoacoustic emissions (DPOAEs in the form of a DP-gram) and Vestibular-evoked myogenic potential (VEMP) immediately before therapy and at the day 10 after therapy. Audio-vestibular adverse effects including hearing loss, tinnitus, vertigo, and otalgia were also considered. RESULTS: Significant elevations in hearing thresholds were found on comparing thresholds at the day 10 at the onset of the study. The elevations were mostly at frequencies (1000, 2000 and 8000Hz) and did not affect speech perception. For DPOAE, significant differences were observed at all F2 frequencies on comparing both amplitudes and signal to noise ratios. Otologic complaints were significant for tinnitus and hearing loss. CONCLUSION: Significant auditory and vestibular adverse effects may result from HMG therapy, indicating the importance of prompt monitoring of auditory functions in these patients.
Asunto(s)
Fármacos para la Fertilidad Femenina/efectos adversos , Pérdida Auditiva/inducido químicamente , Menotropinas/efectos adversos , Acúfeno/inducido químicamente , Adulto , Audiometría de Tonos Puros , Umbral Auditivo/fisiología , Dolor de Oído/inducido químicamente , Dolor de Oído/fisiopatología , Femenino , Fármacos para la Fertilidad Femenina/uso terapéutico , Pérdida Auditiva/fisiopatología , Humanos , Infertilidad Femenina/tratamiento farmacológico , Menotropinas/uso terapéutico , Emisiones Otoacústicas Espontáneas/fisiología , Inducción de la Ovulación/métodos , Estudios Prospectivos , Relación Señal-Ruido , Percepción del Habla/fisiología , Acúfeno/fisiopatología , Vértigo/inducido químicamente , Vértigo/fisiopatología , Potenciales Vestibulares Miogénicos Evocados/fisiología , Adulto JovenRESUMEN
OBJECTIVE: Data on the incidence and severity of ovarian hyperstimulation syndrome (OHSS) in France are limited. METHODS: Prospective observational multicentric study (23 French centers of IVF) in a cohort of 421 women treated with highly purified hMG (HP-hMG) for the first or second cycle of IVF with or without ICSI. The primary objective was to assess the incidence of moderate to severe OHSS in this cohort. RESULTS: At inclusion, 172 patients (40.9%) were considered at risk of OHSS by the physicians. The main measures for risk minimization taken by the physicians rested on initial dose of HP-hMG and protocol choice. At the end of the follow-up (4 months in average), the rate of OHSS moderate to severe was 2.4% (confidence interval 95%: 1.1-4.3%) for the studied IVF cycle. OHSS was severe for 3 women (0.7%) and moderate for 7 women (1.7%). CONCLUSION: This rate of OHSS after IVF is at the lower limit of the rates reported in the literature for OHSS. This study brings reassuring epidemiological data on the rate of OHSS in women at risk. The measures taken by the physicians to minimize the risk of OHSS could have contributed to this low incidence.
Asunto(s)
Fertilización In Vitro/métodos , Menotropinas/administración & dosificación , Síndrome de Hiperestimulación Ovárica/epidemiología , Inducción de la Ovulación/métodos , Adulto , Femenino , Francia/epidemiología , Humanos , Menotropinas/efectos adversos , Síndrome de Hiperestimulación Ovárica/etiología , Inducción de la Ovulación/efectos adversos , Estudios Prospectivos , Factores de Riesgo , Inyecciones de Esperma IntracitoplasmáticasRESUMEN
In this prospective, controlled, randomized, multicentre, non-inferiority study, efficacy and safety of two HMG preparations (Menopur®- Ferring and Meriofert®- IBSA Institut Biochimique SA) for ovarian stimulation were compared (270 women undergoing IVF aged between 18 and 39 years; BMI 30 kg/m2 or less; less than three prior completed assisted reproduction technique cycles). A standard long down-regulation with gonadotrophin-releasing hormone agonist protocol, with HCG triggering was used; primary end-point was total number of oocytes retrieved; attention was paid toovarian hyperstimulation syndrome (OHSS). No statistically significant differences between the treatment groups were reported for most of the clinically significant end-points, including embryo quality, fertilization rate, implantation rate, ongoing pregnancy rate and live birth rate. Total number of oocytes retrieved was higher in the new HMG group compared with the reference (11.6 ± 6.6 and 9.7 ± 5.9, respectively, with a 95% CI of the difference equal +0.43 to +3.43). Increased number of oocytes was obtained through a shorter stimulation, but HMG units per oocyte retrieved were equivalent. The safety profile of the products for frequency of ovarian hyperstimulation syndrome was the same. This study showed that the new HMG preparation is a viable alternative for conducting ovarian stimulation in IVF cycles.
Asunto(s)
Gonadotropina Coriónica/uso terapéutico , Fármacos para la Fertilidad Femenina/uso terapéutico , Menotropinas/uso terapéutico , Inducción de la Ovulación , Adulto , Gonadotropina Coriónica/efectos adversos , Dinamarca , Femenino , Fármacos para la Fertilidad Femenina/efectos adversos , Francia , Humanos , Hungría , Menotropinas/efectos adversos , Recuperación del Oocito , Síndrome de Hiperestimulación Ovárica/epidemiología , Suiza , Resultado del Tratamiento , Reino UnidoRESUMEN
Ovarian hyperstimulation syndrome (OHSS) following gonadotropin-releasing hormone agonist (GnRH-a) trigger is rare. Here, we report a case of severe OHSS after combined GnRH-a and low-dose human chorionic gonadotropin (hCG) trigger in a patient with a single kidney. The patient is a 32-year-old women with a two-year history of infertility. The patient's history was significant for a single kidney, that is, she had donated a kidney to a family member three years ago. The patient underwent controlled ovarian stimulation (COS) for in vitro fertilization (IVF) and received a combined 2 mg GnRH-a and 1500 IU hCG ovulatory trigger. Estradiol (E2) levels on the day of and after the trigger were 3800 pg/mL and 4001 pg/mL, respectively. Four days after the trigger, the patient began experiencing nausea, abdominal distention and dyspnea, and her blood testing revealed hemoconcentration (hemoglobin: 16.9 g/dL; hematocrit: 51.0%) and an elevated creatinine level (1.16 mg/dL). Fresh embryo transfer was deferred. The patient was admitted to the hospital for fluid monitoring and prophylactic anticoagulation. Following inpatient management, her hemoglobin, hematocrit and creatinine levels normalized. The current report highlights that the systemic effects of OHSS can be accentuated in patients with preexisting renal disease or a single kidney.
Asunto(s)
Gonadotropina Coriónica/efectos adversos , Fármacos para la Fertilidad Femenina/efectos adversos , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Antagonistas de Hormonas/efectos adversos , Nefrectomía/efectos adversos , Síndrome de Hiperestimulación Ovárica/etiología , Inducción de la Ovulación/efectos adversos , Adulto , Terapia Combinada , Femenino , Hormona Folículo Estimulante Humana/efectos adversos , Hormona Liberadora de Gonadotropina/efectos adversos , Hormona Liberadora de Gonadotropina/análogos & derivados , Humanos , Infertilidad Femenina/complicaciones , Infertilidad Femenina/terapia , Leuprolida/efectos adversos , Donadores Vivos , Menotropinas/efectos adversos , Recuperación del Oocito/efectos adversos , Síndrome de Hiperestimulación Ovárica/complicaciones , Síndrome de Hiperestimulación Ovárica/fisiopatología , Síndrome de Hiperestimulación Ovárica/terapia , Proteínas Recombinantes/efectos adversos , Insuficiencia Renal/complicaciones , Insuficiencia Renal/terapia , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: To identify the risk factors for suboptimal response to GnRH agonist (GnRH-a) trigger and evaluate the effect of hCG on the outcome of patients with suboptimal response to GnRH-a. DESIGN: A retrospective data analysis. SETTING: A tertiary-care academic medical center. PATIENT(S): A total of 8,092 women undergoing 8,970 IVF/intracytoplasmic sperm injection (ICSI) treatment cycles. INTERVENTION(S): All women underwent hMG + medroxyprogesterone acetate (MPA)/P treatment cycles during IVF/ICSI, which were triggered using a GnRH-a alone or in combination with hCG (1,000, 2,000, or 5,000 IU). Viable embryos were cryopreserved for later transfer. MAIN OUTCOME MEASURE(S): The rates of oocyte retrieval, mature oocytes, fertilization, and the number of oocytes retrieved, mature oocytes, and embryos frozen. RESULT(S): In total, 2.71% (243/8,970) of patients exhibited a suboptimal response to GnRH-a. The suboptimal responders (LH ≤15 mIU/mL) had a significantly lower oocyte retrieval rate (48.16% vs. 68.26%), fewer mature oocytes (4.10 vs. 8.29), and fewer frozen embryos (2.32 vs. 3.54) than the appropriate responders. Basal LH levels served as the single most valuable marker for differentiating suboptimal responders with the areas under the receiver operating curve of 0.805. Administering dual trigger (GnRH-a and hCG 1,000, 2,000, 5,000 IU) significantly increased oocyte retrieval rates (60.04% vs. 48.16%; 68.13% vs. 48.16%; and 65.76% vs. 48.16%, respectively) in patients with a suboptimal response. CONCLUSION(S): Basal LH level was useful predictor of the suboptimal response to GnRH-a trigger. Administrating dual trigger including 1,000 IU hCG for final oocyte maturation could improve the oocytes retrieval rate of GnRH-a suboptimal responder.
Asunto(s)
Gonadotropina Coriónica/administración & dosificación , Fármacos para la Fertilidad Femenina/administración & dosificación , Hormona Liberadora de Gonadotropina/agonistas , Infertilidad/terapia , Acetato de Medroxiprogesterona/administración & dosificación , Menotropinas/administración & dosificación , Recuperación del Oocito , Oocitos/efectos de los fármacos , Inducción de la Ovulación/métodos , Ovulación/efectos de los fármacos , Progesterona/administración & dosificación , Adulto , Área Bajo la Curva , Biomarcadores/sangre , Gonadotropina Coriónica/efectos adversos , Criopreservación , Quimioterapia Combinada , Femenino , Fertilidad/efectos de los fármacos , Fármacos para la Fertilidad Femenina/efectos adversos , Fertilización In Vitro , Humanos , Infertilidad/diagnóstico , Infertilidad/fisiopatología , Hormona Luteinizante/sangre , Acetato de Medroxiprogesterona/efectos adversos , Menotropinas/efectos adversos , Oocitos/metabolismo , Inducción de la Ovulación/efectos adversos , Valor Predictivo de las Pruebas , Progesterona/efectos adversos , Curva ROC , Estudios Retrospectivos , Inyecciones de Esperma Intracitoplasmáticas , Resultado del TratamientoRESUMEN
This preliminary study examined a possible effect of long duration repeated hormonal stimulation on the endometrium using a molecular tool. The expression of the hormone stimulated, cell cycle regulators, p27 and its ligase S-phase kinase-interacting protein2 (Skp2), were assessed in 46 endometrial samples of patients who underwent repeated IVF cycles (3-21). Skp2 protein is usually undetectable in normal tissue and can be demonstrated only in rapidly dividing cells. Samples from non-stimulated, normal cycling women served as control group A. Samples of endometrial carcinoma served as control group B. In secretory endometrium, the expression of p27 was found to be lower and Skp2 higher in the study group compared with control group A. Moreover, in 25% of patients of the study group, Skp2 expression was significantly higher (P < 0.05) compared with control group A, reaching concentrations demonstrated in endometrial carcinoma. The findings of this study suggest that repeated hormone stimulation cycles may disrupt endometrial physiology, potentially towards abnormal proliferation. These changes in protein expression are described for the first time in IVF patients and should be further investigated.
Asunto(s)
Endometrio/efectos de los fármacos , Inducción de la Ovulación , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Adulto , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Endometrio/metabolismo , Endometrio/patología , Femenino , Hormona Folículo Estimulante/efectos adversos , Hormona Folículo Estimulante/uso terapéutico , Humanos , Menotropinas/efectos adversos , Menotropinas/uso terapéutico , Nafarelina/efectos adversos , Nafarelina/uso terapéuticoRESUMEN
OBJECTIVE: To compare the outcomes of controlled ovarian stimulation/in vitro fertilization cycles using 450 IU and 600 IU gonadotropin per day in women at risk of poor ovarian response. DESIGN: Prospective randomized controlled nonblinded study. SETTING: University-affiliated private IVF center. PATIENT(S): Women considered to be at risk of poor ovarian response: aged <41 years with basal FSH >10 IU/L, antimüllerian hormone <1 ng/mL, antral follicle count ≤ 8, or a previous IVF cycle with ≥ 300 IU/d gonadotropin that resulted in a cancellation, <8 follicles, or <5 oocytes. INTERVENTION(S): A total of 356 patients underwent a microdose GnRH agonist flare-up IVF/intracytoplasmic sperm injection protocol with a fixed daily dose of either 450 IU FSH (n = 176) or 600 IU FSH (n = 180) equally divided between Menopur and Bravelle. MAIN OUTCOME MEASURE(S): Number of mature oocytes retrieved. RESULT(S): The two groups were similar in terms of age, ovarian reserve, cause of infertility, duration of stimulation, and cycle cancellation rate. There were no significant differences in the number of metaphase II oocytes retrieved (4 [range 0-6] vs. 4 [range 2-7]), fertilization rate (62.4% vs. 57.0%), biochemical pregnancy rate (20.5% vs. 22.9%), clinical pregnancy rate (16.4% vs. 18.3%), and implantation rate (29.8% vs. 30.4%) between the 450 IU and 600 IU groups, respectively. CONCLUSION(S): Gonadotropin of 600 IU/d does not improve outcome of IVF cycles compared with 450 IU/d in women at risk of poor ovarian response. CLINICAL TRIAL REGISTRATION NUMBER: NCT00971152.
Asunto(s)
Fármacos para la Fertilidad Femenina/administración & dosificación , Hormona Folículo Estimulante/administración & dosificación , Infertilidad/terapia , Menotropinas/administración & dosificación , Ovario/efectos de los fármacos , Inducción de la Ovulación/métodos , Ovulación/efectos de los fármacos , Urofolitropina/administración & dosificación , Adulto , Implantación del Embrión , Transferencia de Embrión , Femenino , Fármacos para la Fertilidad Femenina/efectos adversos , Fertilización In Vitro , Hormona Folículo Estimulante/efectos adversos , Humanos , Infertilidad/diagnóstico , Infertilidad/fisiopatología , Menotropinas/efectos adversos , Recuperación del Oocito , Ovario/fisiopatología , Inducción de la Ovulación/efectos adversos , Embarazo , Índice de Embarazo , Estudios Prospectivos , Quebec , Inyecciones de Esperma Intracitoplasmáticas , Resultado del Tratamiento , Urofolitropina/efectos adversosRESUMEN
OBJECTIVE: To report a case of a substance-induced psychotic disorder secondary to ovulation induction therapy with gonadotrophins. METHOD: Case report. RESULTS: We report a case of a psychotic episode secondary to gonadotrophins therapy. The acute episode was treated with antipsychotic (Aripiprazole). After 2 years the patient remains free of psychotic symptoms. CONCLUSION: There have been several reports correlating low levels of estrogen with psychotic symptoms, leading to studies evaluating the possible effect of this hormone as an antipsychotic. In this case, we report psychotic symptoms with high levels of estradiol, which is contrary to that theory.
Asunto(s)
Fármacos para la Fertilidad Femenina/efectos adversos , Hormona Folículo Estimulante Humana/efectos adversos , Infertilidad Femenina/tratamiento farmacológico , Menotropinas/efectos adversos , Psicosis Inducidas por Sustancias/etiología , Adulto , Femenino , Humanos , Proteínas Recombinantes/efectos adversosRESUMEN
The aim was to compare ovarian response and clinical outcome of potential high-responders after stimulation with highly purified menotropin (HP-hMG) or recombinant follicle-stimulating hormone (rFSH) for in vitro fertilisation/intracytoplasmic sperm injection. Retrospective analysis was performed on data collected in two randomized controlled trials, one conducted following a long GnRH agonist protocol and the other with an antagonist protocol. Potential high-responders (n = 155 and n = 188 in the agonist and antagonist protocol, respectively) were defined as having an initial anti-Müllerian hormone (AMH) value >75th percentile (5.2 ng/ml). In both protocols, HP-hMG stimulation in women in the high AMH category was associated with a significantly lower occurrence of high response (≥15 oocytes retrieved) than rFSH stimulation; 33% versus 51% (p = 0.025) and 31% versus 49% (p = 0.015) in the long agonist and antagonist protocol, respectively. In the potential high-responder women, trends for improved live birth rate were observed with HP-hMG compared with rFSH (long agonist protocol: 33% versus 20%, p = 0.074; antagonist protocol: 34% versus 23%, p = 0.075; overall population: 34% versus 22%, p = 0.012). In conclusion, the type of gonadotropin used for ovarian stimulation influences high-response rates and potentially clinical outcome in women identified as potential high-responders.
Asunto(s)
Hormona Antimülleriana/sangre , Fármacos para la Fertilidad Femenina/efectos adversos , Hormona Folículo Estimulante Humana/efectos adversos , Menotropinas/efectos adversos , Síndrome de Hiperestimulación Ovárica/epidemiología , Ovario/efectos de los fármacos , Inducción de la Ovulación/efectos adversos , Adulto , Biomarcadores/sangre , Transferencia de Embrión , Femenino , Fertilización In Vitro , Hormona Folículo Estimulante Humana/genética , Hormona Liberadora de Gonadotropina/agonistas , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Humanos , Infertilidad Femenina/terapia , Nacimiento Vivo , Síndrome de Hiperestimulación Ovárica/sangre , Ovario/metabolismo , Ovario/fisiopatología , Embarazo , Proteínas Recombinantes/efectos adversos , Estudios Retrospectivos , Riesgo , Inyecciones de Esperma Intracitoplasmáticas , Regulación hacia ArribaRESUMEN
The aim of this multicentre, prospective, randomised, investigator blind, controlled clinical trial was to evaluate the clinical efficacy and tolerability of a highly purified human menopausal gonadotrophin (hMG) preparation (Merional-HG) when administered to patients undergoing controlled ovarian stimulation (COS) for in-vitro fertilisation (IVF) procedure enrolled in hospital departments. One hundred fifty-seven patients were randomised in two parallel groups: 78 started COS with Merional-HG and 79 with Menopur. Results of the study showed that both highly purified hMG preparations were equivalent in terms of number of oocytes retrieved (primary endpoint: 8.8 ± 3.9 versus 8.4 ± 3.8, p = 0.54). In the patients treated with Merional-HG, we observed a higher occurrence of mature oocytes (78.3% versus 71.4%, p = 0.005) and a reduced quantity of gonadotrophins administered per cycle (2.556 ± 636 IU versus 2.969 ± 855 IU, p < 0.001). Fertilisation, cleavage, implantation rates and the number of positive ß-human chorionic gonadotrophin (hCG; pregnancy) tests and the clinical pregnancy rate were comparable in the two groups. Both treatments were well tolerated. In conclusion, the results of this study support the efficacy and safety of Merional-HG administered subcutaneously for assisted reproduction techniques. Efficiency of Merional-HG appears to be higher due to reduced quantity of drug used and the higher yield of mature oocytes retrieved.
Asunto(s)
Fármacos para la Fertilidad Femenina/administración & dosificación , Fármacos para la Fertilidad Femenina/efectos adversos , Fertilización In Vitro , Infertilidad Femenina/terapia , Menotropinas/administración & dosificación , Inducción de la Ovulación/métodos , Adulto , Femenino , Humanos , Inyecciones Subcutáneas , Menotropinas/efectos adversos , Embarazo , Índice de Embarazo , Método Simple Ciego , Resultado del TratamientoRESUMEN
OBJECTIVE: To explore the comparative efficacy, safety, and tolerability of agents used for ovarian stimulation and luteal support when applied in a population of women undergoing in vitro fertilization (IVF) using a gonadotropin-releasing hormone (GnRH) antagonist protocol. STUDY DESIGN: A phase 4, multicenter, randomized, open-label, exploratory clinical trial was performed at 7 assisted reproductive technology centers in the United States. Subjects included 173 women aged 18-42 years with a documented history of infertility who were undergoing IVF. Subjects were randomized to treatment with highly purified human menopausal gonadotropin (HP-hMG) or recombinant human follicle-stimulating hormone (rhFSH) for ovarian stimulation and progesterone vaginal inserts (PVIs) or intramuscular injection of progesterone in oil (PIO) for luteal support. Protocols for IVF followed the standard practices of participating centers within the parameters of the study. RESULTS: Biochemical, clinical, and ongoing pregnancy rates were the main outcome measures. Ongoing pregnancy rates for individual treatment groups ranged from 44.0-46.9%. No statistically significant differences were observed in pregnancy outcomes for the comparisons of HP-hMG vs. rhFSH or PVI vs. PIO. All study medications were generally safe and well tolerated. CONCLUSION: In this study HP-hMG and rhFSH were equally effective for ovarian stimulation during GnRH antagonist IVF cycles. Both PVI and PIO are viable options for luteal support.
Asunto(s)
Fármacos para la Fertilidad Femenina/uso terapéutico , Fertilización In Vitro , Hormona Folículo Estimulante/uso terapéutico , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Infertilidad Femenina/tratamiento farmacológico , Menotropinas/uso terapéutico , Progesterona/administración & dosificación , Adolescente , Adulto , Mantenimiento del Cuerpo Lúteo , Femenino , Fármacos para la Fertilidad Femenina/administración & dosificación , Fármacos para la Fertilidad Femenina/efectos adversos , Hormona Folículo Estimulante/efectos adversos , Humanos , Menotropinas/efectos adversos , Inducción de la Ovulación , Embarazo , Índice de Embarazo , Progesterona/efectos adversos , Adulto JovenRESUMEN
A cohort of patients addressed to a mild stimulation protocol was retrospectively analysed aiming at evaluating the effect of a luteinizing hormone (LH) activity containing stimulation compared to a pure follicle-stimulating hormone (FSH) drive in absence of any pituitary suppression. Due to a referral bias, the two groups (human FSH (hFSH) n = 210; hMG n = 105) were imbalanced for age with the hFSH group (mean age 38.4) being significantly older than the hMG group (mean age 36.8). But the clinical pregnancy rates (20%) did not differ between the groups. Secondary outcome variables showed a higher number of oocytes retrieved (3.02 vs. 2.31) and higher estradiol levels (1148 vs. 820) in the hMG/younger group whereas the fertilization rate (FR) was higher (54.8 vs. 63.8) in the FSH older/group. In spite of the LH content in the hMG product (~10 IU per vial), the LH concentration on the day of human chorionic gonadotropin (hCG) was higher, although non-significantly, in the hFSH group. We suppose hCG contained in hMG inhibited to some extent the natural release of LH from the non-suppressed pituitary. Concluding, the mild stimulation clinical pregnancy rates are satisfactory independently of the treatment choice. The hMG group showed a trend for a lower efficacy. This phenomenon might be limited to non suppressed cycles, but should be taken in due account also when designing full dose controlled ovarian hyperstimulation (COH) treatments.
Asunto(s)
Fármacos para la Fertilidad Femenina/efectos adversos , Fertilización In Vitro , Infertilidad Femenina/terapia , Hormona Luteinizante/efectos adversos , Ovario/efectos de los fármacos , Inducción de la Ovulación/métodos , Hipófisis/efectos de los fármacos , Adulto , Gonadotropina Coriónica/efectos adversos , Gonadotropina Coriónica/farmacología , Estudios de Cohortes , Combinación de Medicamentos , Femenino , Fármacos para la Fertilidad Femenina/farmacología , Hormona Folículo Estimulante Humana/efectos adversos , Hormona Folículo Estimulante Humana/farmacología , Humanos , Italia/epidemiología , Hormona Luteinizante/farmacología , Menotropinas/efectos adversos , Menotropinas/farmacología , Donación de Oocito , Recuperación del Oocito , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Inyecciones de Esperma IntracitoplasmáticasRESUMEN
OBJECTIVE: To compare the efficacy and safety of highly purified menotropin (hphMG) and recombinant FSH (rFSH) for controlled ovarian stimulation in a GnRH antagonist cycle with compulsory single-blastocyst transfer. DESIGN: Randomized, open-label, assessor-blind, parallel groups, multicenter, noninferiority trial. SETTING: Twenty-five infertility centers in seven countries. PATIENT(S): Seven hundred forty-nine women. INTERVENTION(S): Controlled ovarian stimulation with hphMG or rFSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer on day 5 in one fresh or subsequent frozen blastocyst replacement in natural cycles initiated within 1 year of each patient's start of treatment. MAIN OUTCOME MEASURE(S): Ongoing pregnancy (primary end point) and live birth rates, as well as pharmacodynamic parameters. RESULT(S): The ongoing pregnancy rate after a fresh cycle was 30% with hphMG versus 27% with rFSH for the per-protocol (PP) population and 29% versus 27% for the intention-to-treat (ITT) population. Noninferiority of hphMG compared to rFSH was established. Considering frozen cycles initiated within 1 year, the cumulative live birth rate for a single stimulation cycle was 40% and 38% for women treated with hphMG and rFSH, respectively (both PP and ITT). Significant differences in pharmacodynamic end points were found between the two gonadotropin preparations. CONCLUSION(S): Highly purified hMG is at least as effective as rFSH in GnRH antagonist cycles with compulsory single-blastocyst transfer. CLINICAL TRIAL REGISTRATION NUMBER: NCT00884221.
Asunto(s)
Fármacos para la Fertilidad Femenina/administración & dosificación , Hormona Folículo Estimulante de Subunidad beta/administración & dosificación , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Antagonistas de Hormonas/administración & dosificación , Infertilidad/terapia , Menotropinas/administración & dosificación , Inducción de la Ovulación/métodos , Transferencia de un Solo Embrión , Adulto , Biomarcadores/sangre , Tasa de Natalidad , Quimioterapia Combinada , Europa (Continente) , Femenino , Fármacos para la Fertilidad Femenina/efectos adversos , Hormona Folículo Estimulante de Subunidad beta/efectos adversos , Hormona Liberadora de Gonadotropina/metabolismo , Antagonistas de Hormonas/efectos adversos , Humanos , Infertilidad/sangre , Menotropinas/efectos adversos , Recuperación del Oocito , Inducción de la Ovulación/efectos adversos , Embarazo , Índice de Embarazo , Progesterona/sangre , Proteínas Recombinantes/administración & dosificación , Factores de Tiempo , Resultado del Tratamiento , TurquíaRESUMEN
BACKGROUND: Previous studies have reported conflicting results for the comparative doses of recombinant follicle stimulating hormone (rFSH) and highly purified human menopausal gonadotrophin (hMG-HP) required per cycle of in vitro fertilisation (IVF); the aim of this study was to determine the average total usage of rFSH versus hMG-HP in a 'real-world' setting using routine clinical practice. METHODS: This retrospective chart review of databases from four European countries investigated gonadotrophin usage, oocyte and embryo yield, and pregnancy outcomes in IVF cycles (± intra-cytoplasmic sperm injection) using rFSH or hMG-HP alone. Included patients met the National Institute for Health and Clinical Excellence (NICE) guideline criteria for IVF and received either rFSH or hMG-HP. Statistical tests were conducted at 5% significance using Chi-square or t-tests. RESULTS: Of 30,630 IVF cycles included in this review, 74% used rFSH and 26% used hMG-HP. A significantly lower drug usage per cycle for rFSH than hMG-HP (2072.53 +/- 76.73 IU vs. 2540.14 +/- 883.08 IU, 22.6% higher for hMG-HP; p < 0.01) was demonstrated. The median starting dose was also significantly lower for rFSH than for hMG-HP (150 IU vs. 225 IU, 50% higher for hMG-HP, p < 0.01). The average oocyte yield per IVF cycle in patients treated with rFSH was significantly greater than with hMG-HP (10.80 +/- 6.02 vs. 9.77 +/- 5.53; p < 0.01), as was the average mature oocyte yield (8.58 +/- 5.27 vs. 7.72 +/- 4.59; p < 0.01). No significant differences were observed in pregnancy outcomes including spontaneous abortion between the two treatments. There was a significantly higher rate of OHSS (all grades) with rFSH (18.92% vs. 14.09%; p < 0.0001). The hospitalisation rate due to OHSS was low but significantly higher in the rFSH group (1.07% of cycles started vs. 0.67% of cycles started with rFSH and hMG-HP, respectively; p = 0.002). CONCLUSIONS: Based on these results, IVF treatment cycles with rFSH yield statistically more oocytes (and more mature oocytes), using significantly less IU per cycle, versus hMG-HP. The incidence of all OHSS and hospitalisations due to OHSS was significantly higher in the rFSH cycles compared to the hMG-HP cycles. However, the absolute incidence of hospitalisations due to OHSS was similar to that reported previously. These results suggest that the perceived required dosage with rFSH is currently over-estimated, and the higher unit cost of rFSH may be offset by a lower required dosage compared with hMG-HP.
Asunto(s)
Fertilización In Vitro/métodos , Hormona Folículo Estimulante/administración & dosificación , Menotropinas/administración & dosificación , Inducción de la Ovulación/métodos , Adulto , Femenino , Hormona Folículo Estimulante/efectos adversos , Humanos , Menotropinas/efectos adversos , Recuperación del Oocito/métodos , Síndrome de Hiperestimulación Ovárica/inducido químicamente , Inducción de la Ovulación/efectos adversos , Inducción de la Ovulación/economía , Embarazo , Resultado del Embarazo , Proteínas Recombinantes/administración & dosificaciónRESUMEN
In this prospective, follow-up study of 102 high-risk oocyte donors in their luteal phase, we found a complete absence of ovarian hyperstimulation syndrome (no signs of hemoconcentration or ascites) after the donors were triggered with a gonadotropin releasing-hormone (GnRH) agonist. Due to its powerful preventive effect, the GnRH antagonist protocol combined with a GnRH agonist trigger should preferentially be used in egg donors; in conjunction with an effective luteal support or embryo cryopreservation, the protocol could also be applied to high-risk in vitro fertilization patients.