RESUMO
BACKGROUND: Non-invasive oocyte quality scoring, based on cumulus gene expression analysis, in combination with morphology scoring, can increase the clinical pregnancy (CPR) and live birth rates (LBR) in Day 3 eSET (elective single embryo transfer) ICSI patients. This was first investigated in a pilot study and is now confirmed in a large patient cohort of 633 patients. It was investigated whether CPR, LBR and time-to-pregnancy could be improved by analyzing the gene expression profile of three predictive genes in the cumulus cells, compared to patients with morphology-based embryo selection only. METHODS: A large interventional, non-randomized, assessor-blinded cohort study with 633 ICSI patients was conducted in a tertiary fertility center. Non-PCOS patients, 22-39 years old, with good ovarian reserve, were stimulated with HP-hMG using a GnRH antagonist protocol and planned for fresh Day 3 eSET. The cumulus cells from individually denuded oocytes were ranked by a lab-developed cumulus cell test: qRT-PCR for three predictive genes (CAMK1D, EFNB2 and SASH1) and two control genes (UBC, B2M). The embryo selected for transfer was highest ranked from the pool of morphologically transferable Day 3 embryos. Patients in the control (n = 520) and experimental arm (n = 113) were compared for clinical pregnancy and live birth, using a weighted generalized linear model, and time-to-pregnancy using Kaplan-Meier curves. RESULTS: The CPR was 61% in the experimental arm (n = 113) vs 29% in the control arm (n = 520, p < 0.0001). The LBR in the experimental arm (50%) was significantly higher than in the control arm (27%,p < 0.0001). Time-to-pregnancy was significantly shortened by 3 transfer cycles independent of the number of embryos available on Day 3 (Kaplan-Meier, p < 0.0001). Cumulus cell tested patients < 35 years (n = 65) or ≥ 35 years (n = 48) had a CPR of 62 and 60% respectively (ns). For cumulus cell tested patients with 2, 3-4, or > 4 transferable embryos, the CPR was 66, 52, and 67% (ns) respectively, and thus independent of the number of transferable embryos on Day 3. CONCLUSIONS: This study provides further evidence of the clinical usefulness of the non-invasive cumulus cell test over time in a larger patient cohort. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03659786 / NCT02962466 (Registered 6Sep2018/11Nov2016, retrospectively registered.
Assuntos
Recuperação de Oócitos/métodos , Transferência de Embrião Único/métodos , Injeções de Esperma Intracitoplásmicas , Adulto , Bélgica , Coeficiente de Natalidade , Estudos de Coortes , Transferência Embrionária/métodos , Feminino , Humanos , Infertilidade/diagnóstico , Infertilidade/terapia , Nascido Vivo , Modelos Teóricos , Oócitos/citologia , Gravidez , Taxa de Gravidez , Método Simples-Cego , Injeções de Esperma Intracitoplásmicas/métodos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
It is widely known that luteinising hormone (LH) and human chorionic gonadotrophin (hCG) are integral in the female reproductive lifecycle. Due to the common binding site and similarity in molecular structure, they were previously thought to have overlapping roles. However, with the development of both purified urinary-derived and recombinant gonadotrophins, the individual characteristics of these molecules have begun to be defined. There is evidence to suggest that LH and hCG preferentially activate different signalling cascades and display different receptor-binding kinetics. The data generated on the two molecules have led to an improved understanding of their distinct physiological functions, resulting in a debate among clinicians regarding the most beneficial use of LH- and hCG-containing products for ovarian stimulation (OS) in assisted reproductive technologies (ARTs). Over the past few decades, a number of trials have generated data supporting the use of hCG for OS in ART. Indeed, the data indicated that hCG plays an important role in folliculogenesis, leads to improved endometrial receptivity and is associated with a higher quality of embryos, while presenting a favourable safety profile. These observations support the increased use of hCG as a method to provide LH bioactivity during OS. This review summarises the molecular and functional differences between hCG and LH, and provides an overview of the clinical trial data surrounding the use of products for OS that contain LH bioactivity, examining their individual effect on outcomes such as endometrial receptivity, oocyte yield and embryo quality, as well as key pregnancy outcomes.
Assuntos
Gonadotropina Coriônica/uso terapêutico , Indução da Ovulação/métodos , Técnicas de Reprodução Assistida , Gonadotropina Coriônica/farmacologia , Feminino , Humanos , Infertilidade/epidemiologia , Infertilidade/terapia , Masculino , Gravidez , Resultado da Gravidez/epidemiologia , Técnicas de Reprodução Assistida/estatística & dados numéricos , Resultado do TratamentoRESUMO
RESEARCH QUESTION: Can a strategy for scoring oocyte quality, based on cumulus cell (CC) gene expression, prioritize oocytes with the highest implantation potential, while limiting the number of embryos to be processed in culture and the number of supernumerary embryos to be vitrified? DESIGN: An interventional, blinded, prospective cohort study was retrospectively analyzed. In the original study, patients underwent a fresh Day3 single embryo transfer with embryos ranked based on morphology and CC gene expression (Aurora Test). The additional ranking of the embryos with the Aurora Test resulted in significant higher clinical pregnancy and live birth rates. Now it is investigated if the Aurora Test ranking could be applied to select oocytes. The effect of an Aurora Test based restriction to 2 and 3 2PN or MII oocytes on clinical pregnancy and other outcomes, was analyzed in two subsets of patients with all 2PN (n = 83) or all MII oocytes (n = 45) ranked. RESULTS: Considering only the top three ranked 2PN oocytes, 95% of the patients would have received a fresh SET on Day3 resulting in 65% clinical pregnancies. This was not different from the pregnancy rate obtained in a strategy using all oocytes but significantly reduced the need for vitrification of supernumerary embryos by 3-fold. Considering only top-ranked MII oocytes gave similar results. CONCLUSIONS: In countries with legal restrictions on freezing of embryos, gene expression of CC can be used for the selective processing of oocytes and would thus decrease the twin pregnancy rate and workload, especially for embryo morphology scoring and transfers as the handling and processing of lower competence oocytes is prevented, while improving the ART outcome.
Assuntos
Células do Cúmulo , Transferência Embrionária , Gravidez , Feminino , Humanos , Congelamento , Estudos Retrospectivos , Estudos Prospectivos , Células do Cúmulo/metabolismo , Oócitos/metabolismo , Taxa de Gravidez , Vitrificação , Criopreservação/métodosRESUMO
BACKGROUND: In women scheduled for cancer treatment, oocytes cryopreservation is a well-established procedure. Random start protocols have been a substantial improvement in this setting, allowing to prevent delay in the initiation of cancer treatments. However, there is still the need to optimize the regimen of ovarian stimulation, to make treatments more patient-friendly and to reduce costs. METHODS: This retrospective study compares two periods (2019 and 2020), corresponding to two different ovarian stimulation regimens. In 2019, women were treated with corifollitropin, recombinant FSH and GnRH antagonists. Ovulation was triggered with GnRH agonists. In 2020, the policy changed, and women were treated with a progestin-primed ovarian stimulation (PPOS) protocol with human menopausal gonadotropin (hMG) and dual trigger (GnRH agonist and low dose hCG) Continuous data are reported as median [Interquartile Range]. To overcome expected changes in baseline characteristics of the women, the primary outcome was the ratio between the number of mature oocytes retrieved and serum anti-mullerian hormone (AMH) in ng/ml. RESULTS: Overall, 124 women were selected, 46 in 2019 and 78 in 2020. The ratio between the number of mature oocytes retrieved and serum AMH in the first and second period was 4.0 [2.3-7.1] and 4.0 [2.7-6.8], respectively (p = 0.80). The number of scans was 3 [3-4] and 3 [2-3], respectively (p<0.001). The total costs of the drugs used for ovarian stimulation were 940 [774-1,096 ] and 520 [434-564 ], respectively (p<0.001). CONCLUSIONS: Random start PPOS with hMG and dual trigger represents an easy and affordable ovarian stimulation protocol for fertility preservation in women with cancer, showing similar efficacy and being more friendly and economical.
Assuntos
Preservação da Fertilidade , Infertilidade Feminina , Neoplasias , Humanos , Feminino , Progestinas/uso terapêutico , Preservação da Fertilidade/métodos , Gonadotropina Coriônica , Estudos Retrospectivos , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Esteroides , Hormônio Liberador de Gonadotropina , Fertilização in vitro/métodosRESUMO
Controversy exists about the risk of microbiological contamination from direct contact with unsterile liquid nitrogen during oocyte vitrification. The aim of this observational study was to evaluate the effectiveness of oocyte vitrification using a high-security closed vitrification system in a donation programme. Oocyte vitrification was performed using CBS High Security closed straws (Cryo Bio System) with DMSO/ethylene glycol/sucrose as the cryoprotectant (Irvine Scientific freeze kit). A total of 123 vitrified metaphase-II oocytes were warmed in 20 recipient cycles (6.2 warmed oocytes per recipient); of these, 111 oocytes (90.2%) survived vitrification and warming. All surviving oocytes were microinjected and 86 (77.5%) were normally fertilized, of which 53 (61.6%) developed up to good-quality day 3. Ten embryo transfers resulted in a clinical pregnancy (50.0%) and an ongoing clinical pregnancy rate of 45%. Five revitrified embryos were warmed in three warming cycles (survival rate 100%). These transfers resulted in an additional ongoing twin pregnancy, leading to a cumulative ongoing pregnancy rate per patient of 50% (10/20). The ongoing implantation rate per warmed oocyte and per injected oocyte was 10.6% (13/123) and 11.7% (13/111). The present data demonstrate that oocyte vitrification using a closed vitrification device yields excellent oocyte survival, fertilization and embryo development.
Assuntos
Doação de Oócitos/métodos , Oócitos , Vitrificação , Criopreservação/métodos , Transferência Embrionária , Feminino , Fertilização in vitro/métodos , Humanos , Gravidez , Taxa de GravidezRESUMO
Evidence regarding the role of anti-Müllerian hormone (AMH) among oocyte donors is limited and only involves gonadotrophin-releasing hormone (GnRH)-agonist-treated donors. This trial assessed the predictive ability of AMH for ovarian response among 108 oocyte donors treated with an antagonist protocol. In multivariate linear regression analysis, both AMH and age were independently associated with ovarian response (unstandardized coefficients 0.904 and -0.378, respectively). In receiver operating characteristic curve analysis, AMH performed better than age, but was a modest predictive marker for low (≤ 6 oocytes) and excessive (>20 oocytes) ovarian response (area under the curve (AUC) 0.643 and 0.695, respectively). Similarly, a multivariate logistic model including AMH and age was also modest (AUC 0.651 and 0.697 for low and excessive responders, respectively). The predictive ability of AMH did not significantly alter when different thresholds were adopted, such as <4 oocytes for low response and >25 for excessive response (AUC 0.759 and 0.724, respectively). Among oocyte donors treated with a GnRH-antagonist protocol, although AMH was correlated with the number of oocytes retrieved, it demonstrates a modest ability in discriminating women with low or excessive ovarian response. Selection of oocyte donors is of paramount importance for the proper and more cost-efficient functionality of the oocyte donation programme. Despite the extensive literature regarding the efficacy of anti-Müllerian hormone (AMH) for predicting ovarian response among infertile patients, available evidence regarding the role of AMH in oocyte donors is considerably limited and involves only agonist down-regulated cycles. In this trial we assessed whether AMH can be considered a predictive marker for ovarian response among oocyte donors treated with a gonadotrophin-releasing hormone (GnRH)-antagonist protocol. According to our results, among oocyte donors treated with a GnRH-antagonist protocol, although AMH was correlated with the number of oocytes retrieved, the correlation is not strong and it appears that AMH has a modest predictive ability to discriminate women who are likely to demonstrate either impaired or excessive response to ovarian stimulation.
Assuntos
Hormônio Antimülleriano/sangue , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Recuperação de Oócitos , Ovário/efeitos dos fármacos , Doadores de Tecidos , Adulto , Biomarcadores/sangue , Estudos de Coortes , Feminino , Hormônio Liberador de Gonadotropina/farmacologia , Humanos , Avaliação de Resultados em Cuidados de Saúde , Indução da Ovulação/métodos , Valor Preditivo dos Testes , Curva ROC , Análise de Regressão , Estudos RetrospectivosRESUMO
UNLABELLED: BACKGROUND The objective of this investigation was to establish independent predictors of follicle-stimulating hormone (FSH) threshold dose in anovulatory women undergoing ovulation induction with FSH preparations. METHODS: One hundred and fifty-one patients with WHO Group II anovulatory infertility failing to ovulate or conceive on clomiphene citrate underwent ovarian stimulation with FSH-only preparations following a low-dose step-up protocol. The individual FSH threshold dose was defined as the FSH dose when meeting the human chorionic gonadotrophin criteria (one follicle > or =17 mm, or 2-3 follicles > or =15 mm). The influence of demographics, physical characteristics, obstetric and infertility and menstrual cycle history, ovarian ultrasonography, endocrine parameters and type of gonadotrophin preparation on the FSH threshold dose was assessed through multiple regression analysis. RESULTS: In the univariate analysis, age, body mass index (BMI), failure to ovulate with clomiphene citrate, menstrual cycle history (amenorrhea, oligomenorrhea or anovulatory cycles of 21-35 days), mean ovarian volume, LH/FSH ratio, testosterone and free androgen index were significant (P < 0.05) predictors of FSH threshold dose. In the multivariate analysis, menstrual cycle history, mean ovarian volume and BMI remained significant (P < 0.001). CONCLUSIONS: The individual FSH threshold dose for ovulation induction in anovulatory women can be predicted based on three variables easily determined in clinical practice: menstrual cycle history, mean ovarian volume and BMI. A FSH dosage nomogram was constructed based on these parameters.
Assuntos
Hormônio Foliculoestimulante/administração & dosagem , Hormônios/administração & dosagem , Infertilidade Feminina/tratamento farmacológico , Ovário/anatomia & histologia , Indução da Ovulação , Adulto , Índice de Massa Corporal , Clomifeno/uso terapêutico , Feminino , Fármacos para a Fertilidade Feminina/uso terapêutico , Previsões , Humanos , Tamanho do Órgão , Ovário/diagnóstico por imagem , Ovulação/efeitos dos fármacos , Índice de Gravidade de Doença , Resultado do Tratamento , UltrassonografiaRESUMO
The objective of this study was to compare the live birth rates resulting from ovarian stimulation with highly purified human menopausal gonadotrophin (HP-HMG), which combines FSH and human chorionic gonadotrophin-driven LH activities, or recombinant FSH (rFSH) alone in women undergoing IVF cycles. An integrated analysis was performed of the raw data from two randomized controlled trials that were highly comparable in terms of eligibility criteria and post-randomization treatment regimens with either HP-HMG or rFSH for ovarian stimulation in IVF, following a long down-regulation protocol. All randomized subjects who received at least one dose of gonadotrophin in an IVF cycle (HP-HMG, n = 491; rFSH, n = 495) were included in the analysis. Subjects who underwent intracytoplasmic sperm injection cycles were excluded. The superiority of one gonadotrophin preparation over the other was tested using the likelihood ratio test in a logistic regression analysis. The live birth rate per cycle initiated was 26.5% (130/491) with HP-HMG and 20.8% (103/495) with rFSH (P = 0.041). The odds ratio in favour of HP-HMG was 1.36 (95% confidence interval: 1.01-1.83). Thus, the findings of this integrated analysis demonstrate that ovarian stimulation with HP-HMG, following a long down-regulation protocol, in IVF cycles results in significantly more live births than stimulation with rFSH alone.
Assuntos
Fertilização in vitro/métodos , Hormônio Foliculoestimulante/uso terapêutico , Menotropinas/isolamento & purificação , Menotropinas/uso terapêutico , Indução da Ovulação/métodos , Adolescente , Adulto , Implantação do Embrião , Feminino , Hormônio Foliculoestimulante/efeitos adversos , Humanos , Menotropinas/efeitos adversos , Menotropinas/química , Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: The luteal phase after ovarian hyperstimulation for in vitro fertilization (IVF) is insufficient. Therefore, luteal phase supplementation is routinely applied in IVF. It may be postulated that premature luteolysis after ovarian hyperstimulation is due to supraphysiological steroid levels in the early luteal phase. In the present study, high doses of steroids are administered after the LH surge in normo-ovulatory volunteers in order to investigate whether this intervention gives rise to endocrine changes and a shortening of the luteal phase. DESIGN: Randomized controlled trial. METHODS: Forty non-smoking, normal weight women, between 18 and 37 years of age, with a regular menstrual cycle (24-35 days), received either high dosages of estradiol (E2), progesterone (P), E2+P or no medication. Blood sampling was performed every other day from the day of the LH surge until LH+14. Duration of the luteal phase and endocrine profiles were the main study outcomes. RESULTS: Early luteal phase steroid concentrations achieved by exogenous administration were comparable with levels observed following ovarian hyperstimulation for IVF. No difference in the luteal phase length was observed comparing all groups. However, a significant decrease in LH levels could be observed 6 days after the mid-cycle LH surge (P<0.001) in women receiving P, resulting in accelerated decrease of inhibin A production by the corpus luteum (P=0.001). CONCLUSION: The present intervention of high-dose steroid administration shortly after the LH surge failed to induce a premature luteolysis regularly in cyclic women. It seems that the induced transient suppression in LH allowed for a timely recovery of corpus luteum function. Other additional factors may be held responsible for the distinct reduction in luteal phase length observed after ovarian hyperstimulation for IVF.
Assuntos
Estradiol/administração & dosagem , Infertilidade Feminina/tratamento farmacológico , Fase Luteal/efeitos dos fármacos , Indução da Ovulação/métodos , Progesterona/administração & dosagem , Adolescente , Adulto , Corpo Lúteo/efeitos dos fármacos , Corpo Lúteo/fisiologia , Estradiol/efeitos adversos , Feminino , Fertilização in vitro , Humanos , Infertilidade Feminina/fisiopatologia , Luteólise/efeitos dos fármacos , Luteólise/fisiologia , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Indução da Ovulação/efeitos adversos , Progesterona/efeitos adversosRESUMO
OBJECTIVE: To determine the aneuploidy rate in embryos of women with idiopathic recurrent miscarriages and to evaluate whether preimplantation genetic diagnosis for aneuploidy screening could be a feasible approach to improve the possibility of successful pregnancy in these couples. DESIGN: Prospective cohort study. SETTING: Tertiary university referral center. PATIENT(S): Women (n = 49) with recurrent idiopathic miscarriages. INTERVENTION(S): In vitro fertilization with preimplantation genetic diagnosis for aneuploidy screening. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate (PR) and aneuploidy rate. RESULT(S): The aneuploidy rate was, respectively, 43.85% and 66.95% in the younger and older group. The ongoing PR per cycle was 25.71% in the younger and 2.94% in the older patients. CONCLUSION(S): There is no therapeutic evidence to prescribe IVF with or without preimplantation genetic diagnosis for aneuploidy screening for this heterogeneous group of patients.
Assuntos
Aborto Habitual/diagnóstico , Aborto Habitual/genética , Aneuploidia , Aberrações Cromossômicas , Diagnóstico Pré-Implantação , Adulto , Feminino , Testes Genéticos , Humanos , Hibridização in Situ Fluorescente , Gravidez , Resultado da Gravidez , Estudos ProspectivosRESUMO
Huntington's disease is an autosomal dominant, late-onset disorder, for which the gene and the causative mutation have been known since 1993. Some at-risk patients choose for presymptomatic testing and can make reproductive choices accordingly. Others however, prefer not to know their carrier status, but may still wish to prevent the birth of a carrier child. For these patients, exclusion testing after prenatal sampling has been an option for many years. A disadvantage of this test is that unaffected pregnancies may be terminated if the parent at risk (50%) has not inherited the grandparental Huntington gene, leading to serious moral and ethical objections. As an alternative, preimplantation genetic diagnosis (PGD) on embryos obtained in vitro may be proposed, after which only embryos free of risk are replaced. Embryos can then be selected, either by the amplification of the CAG repeat in the embryos without communicating results to the patients (ie non-disclosure testing), which brings its own practical and moral problems, or exclusion testing. We describe here the first PGD cycles for exclusion testing for Huntington's disease in five couples. Three couples have had at least one PGD cycle so far. One pregnancy ensued and a healthy female baby was delivered.
Assuntos
Doença de Huntington/diagnóstico , Diagnóstico Pré-Implantação , Feminino , Heterozigoto , Humanos , Doença de Huntington/genética , Técnicas In Vitro , Masculino , LinhagemRESUMO
Additional analysis of a multinational, open-label, randomized study comparing highly purified hMG and recombinant FSH in a long protocol revealed that LH activity might favorably influence pregnancy outcome in IVF cycles.
Assuntos
Fertilização in vitro , Injeções de Esperma Intracitoplásmicas , Gonadotropina Coriônica/sangue , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/farmacologia , Humanos , Hormônio Luteinizante/sangue , Masculino , Menotropinas/farmacologia , Gravidez , Resultado do TratamentoRESUMO
OBJECTIVE: To report the first pregnancy and live birth after ovarian stimulation using a chimeric long-acting human recombinant FSH agonist (recFSH-CTP) for IVF. DESIGN: Case report. SETTING: Tertiary fertility center. PATIENT(S): A 32-year-old woman with a 7-year history of primary infertility. INTERVENTION(S): Ovarian stimulation with a single SC injection of 180 microg recFSH-CTP on cycle day 3, followed by daily injections of 150 IU recFSH from cycle day 10 onward, combined with daily GnRH antagonist 0.25 mg SC to prevent a premature LH rise. Final oocyte maturation was induced by 10,000 IU hCG. MAIN OUTCOME MEASURE(S): First ongoing pregnancy obtained with recFSH-CTP. RESULT(S): Twelve oocytes were retrieved. Ten oocytes were fertilized in vitro by intracytoplasmic sperm injection, and from these 10 oocytes, two embryos were subsequently transferred after 3 days of culture. A pregnancy test 2 weeks after ET was positive, and ultrasound investigation revealed an intact, intrauterine, singleton pregnancy after 12 weeks. CONCLUSION(S): The first pregnancy and live birth was achieved after ovarian stimulation using recFSH-CTP for IVF.
Assuntos
Hormônio Foliculoestimulante Humano , Hormônio Foliculoestimulante/uso terapêutico , Hormônio Liberador de Gonadotropina/análogos & derivados , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Adulto , Gonadotropina Coriônica/administração & dosagem , Transferência Embrionária , Feminino , Hormônio Foliculoestimulante/administração & dosagem , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/administração & dosagem , Humanos , Injeções Subcutâneas , Gravidez , Proteínas Recombinantes/uso terapêutico , Injeções de Esperma IntracitoplásmicasRESUMO
OBJECTIVE: To investigate the effect of ovarian stimulation on integrin expression in the early luteal phase. STUDY DESIGN: Seven endometrial biopsies were taken 2 days after the oocyte retrieval from stimulated cycles for IVF and 23 from natural cycles, 2 days after ovulation. RESULT: Endometrium was in-phase in 22/23 and 7/7 biopsies from the natural and stimulated cycles, respectively. Integrins alpha(1) and alpha(4) were simultaneously positive in 43.4% from the natural and in all (100%) the stimulated cycles (P<0.03). On the day of the endometrial biopsy, progesterone serum values were higher in the stimulated cycles (55.2+/-9.5 microg/l versus 8.5+/-3.8 microg/l) (P<0.001). HSCORE value was significantly higher in stimulated cycles for both integrins. CONCLUSION: Endometrial integrin expression is more consistently present in the early luteal phase in stimulated cycles than in natural cycles and this may be related to the higher serum progesterone concentration and/or the more advanced endometrial histological features.
Assuntos
Endométrio/química , Fertilização in vitro , Integrinas/análise , Fase Luteal , Indução da Ovulação , Ovulação , Adulto , Biópsia , Feminino , Humanos , Imuno-Histoquímica , Integrina alfa1/análise , Integrina alfa4/análise , Oócitos , Gravidez , Progesterona/sangue , Coleta de Tecidos e ÓrgãosAssuntos
Endométrio/citologia , Endométrio/efeitos dos fármacos , Oócitos , Indução da Ovulação , Doadores de Tecidos , Coleta de Tecidos e Órgãos , Adulto , Feminino , Hormônio Foliculoestimulante/uso terapêutico , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Fase Luteal , Ciclo Menstrual/efeitos dos fármacos , Mitose/efeitos dos fármacos , Proteínas Recombinantes/uso terapêuticoRESUMO
Allogeneic hematopoietic stem cell transplantation from an human leukocyte antigen (HLA)-identical donor is currently the only proven curative treatment for chronic granulomatous disease. Hematopoietic stem cell transplantation with alternative donors is associated with higher morbidity and mortality. Therefore, we performed in vitro fertilization and preimplantation HLA matching combined with female sexing for hematopoietic stem cell transplantation in chronic granulomatous disease. Ethical and psychological issues were considered carefully. We used in vitro fertilization with X-enriched spermatozoa followed by preimplantation genetic diagnosis to identify female HLA-genoidentical embryos in a family in need of a suitable donor for their boy affected with severe X-linked chronic granulomatous disease. Two preimplantation genetic diagnosis cycles were performed in the family. In the second cycle, 2 HLA-genoidentical female embryos were transferred and a singleton pregnancy was obtained, resulting in the birth of an unaffected girl at term. Because of insufficient cell numbers in the cord-blood source, conventional hematopoietic stem cell transplantation had to be performed at 12 months of age of the donor and 5 years of age of the recipient and resulted in complete stable donor chimerism and immunologic reconstitution up to 25 months post-hematopoietic stem cell transplantation. Hematopoietic stem cell transplantation after in vitro fertilization and combined female sexing and HLA matching offers a new and relatively rapid therapeutic option for patients with X-linked primary immunodeficiency such as chronic granulomatous disease who need hematopoietic stem cell transplantation but lack an HLA-genoidentical donor.
Assuntos
Transplante de Medula Óssea/métodos , Doença Granulomatosa Crônica/cirurgia , Antígenos HLA/imunologia , Teste de Histocompatibilidade/métodos , Diagnóstico Pré-Implantação/métodos , Reimplante/métodos , Adulto , Pré-Escolar , Feminino , Seguimentos , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/imunologia , Humanos , Lactente , Masculino , GravidezRESUMO
BACKGROUND: The objective of this study was to demonstrate non-inferiority of a highly purified urinary follicle stimulating hormone (HP-FSH) preparation compared with a recombinant (rFSH) preparation with respect to ovulation rate (primary end-point). METHODS: This was a randomized, open-label, assessor-blind, multinational study. Women with anovulatory infertility WHO Group II and resistant to clomiphene citrate were randomized (computer-generated list) to stimulation with HP-FSH (n=73) or rFSH (n=78) using a low-dose step-up protocol. The non-inferiority limit was prespecified at -20%. RESULTS: The ovulation rate was 85.2% (51/62) with HP-FSH and 90.9% (60/66) with rFSH (per-protocol population), and non-inferiority was demonstrated [95% confidence interval: -16.9; 5.6]. No differences were noted between groups in number of follicles>or=12 mm, >or=15 mm or >or=18 mm, mono-follicular development, pregnancy rates, endometrial thickness, number of ovarian stimulation syndrome cases or frequency of injection site reactions/pain. The singleton live birth rate was 15% in both groups (11/73 with HP-FSH and 12/78 with rFSH). CONCLUSIONS: This urinary HP-FSH preparation is non-inferior compared with a rFSH preparation with respect to ovulation rate in anovulatory WHO Group II women failing to ovulate or conceive on clomiphene citrate.
Assuntos
Hormônio Foliculoestimulante/uso terapêutico , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Clomifeno/uso terapêutico , Feminino , Subunidade beta do Hormônio Folículoestimulante/química , Humanos , Ovulação/efeitos dos fármacos , Gravidez , Isoformas de Proteínas , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the safety of applying follicular-fluid meiosis-activating sterol (FF-MAS) in vitro to immature human oocytes. DESIGN: Phase I bicenter, randomized, parallel-group, controlled, partially blinded trial. SETTING: Third-level referral academic centers, including reproductive biology and genetics laboratories. PATIENTS: Endocrinologically normal women with a medical indication for IVF or intracytoplasmic sperm injection, or healthy volunteers. INTERVENTION(S): Subjects were randomized at a ratio 1 to 6 into either conventional GnRH-agonist and recombinant FSH stimulation (IVO) for oocyte retrieval, or minimally stimulated in vitro maturation (IVM) with the use of recombinant FSH. Retrieved immature oocyte cumulus complexes were cultured for 30 or 36 hours in one of six IVM culture conditions containing FF-MAS (range, 0.1-20 microM). Polar body-extruded oocytes from the IVO and IVM groups were processed for chromosomal analysis. MAIN OUTCOME MEASURE(S): The primary endpoint was the incidence of metaphase II stage oocytes with numeric chromosomal abnormalities, using full (spectral karyotyping) or partial (fluorescent in situ hybridization with seven probes) karyotyping or Giemsa count. A secondary objective was to document the frequency of metaphase II oocytes after IVM with FF-MAS supplements. RESULT(S): Oocyte cumulus complexes obtained from the IVO (mean, 8.9) and IVM (mean, 6.2) groups had equal maturation rates. Compared to IVO, exposure of germinal-vesicle oocytes for a maturation period of 30 hours did not increase aneuploidy. An exposure period of 36 hours doubled the aneuploidy rate, but this was significant only for the 20-muM dose of FF-MAS. CONCLUSION: Inclusion of 1-10 microM FF-MAS in a 30-hour IVM protocol is safe.
Assuntos
Colestenos/efeitos adversos , Oócitos/efeitos dos fármacos , Adulto , Aneuploidia , Aberrações Cromossômicas , Feminino , Fertilização in vitro , Hormônio Foliculoestimulante , Humanos , Técnicas In Vitro , Meiose , Oócitos/fisiologia , Oócitos/ultraestrutura , Injeções de Esperma IntracitoplásmicasRESUMO
BACKGROUND: The contribution of the LH activity in menotrophin preparations for ovulation induction has been investigated in small trials conducted versus FSH preparations. The objective of this study was to demonstrate non-inferiority of highly purified urinary menotrophin (HP-HMG) versus recombinant FSH (rFSH) with respect to the primary outcome measure, ovulation rate. METHODS: This was a randomized, open-label, assessor-blind, multinational study. Women with anovulatory infertility WHO Group II and resistant to clomiphene citrate were randomized (computer-generated list) to stimulation with HP-HMG (n=91) or rFSH (n=93) using a low-dose step-up protocol. RESULTS: The ovulation rate was 85.7% with HP-HMG and 85.5% with rFSH (per-protocol population), and non-inferiority was demonstrated. Significantly fewer intermediate-sized follicles were observed in the HP-HMG group (P<0.05). The singleton live birth rate was comparable between the two groups. The frequency of ovarian hyperstimulation syndrome and/or cancellation due to excessive response was 2.2% with HP-HMG and 9.8% with rFSH (P=0.058). CONCLUSIONS: Stimulation with HP-HMG is associated with ovulation rates at least as good as a rFSH in anovulatory WHO Group II women. LH activity modifies follicular development so that fewer intermediate-sized follicles develop. This could have a positive impact on the safety of ovulation induction protocols.